- Palladium on carbon encapsulated in POEPOP1500: A resin-supported catalyst for hydrogenation reactions
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(formula presented) A new a versatile catalyst for hydrogenation reactions wherein palladium on arbon is encapsulated in POEPOP1500-resin is described. This polymer-supported catalyst has been successfully used in solution phase hydrogenation of a double and a triple bond as well as hydrogenolysis of a benzyl-protecting group. While the activity of the new catalyst is marginally lower than standard 10% Pd/C, it has the advantage of being reused several times without significant loss of reactivity.
- Jansson, Anita M.,Grotli, Morten,Halkes, Koen M.,Meldal, Morten
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Read Online
- An efficient synthesis of N-tert-butoxycarbonyl-O-cyclohexyl-L-tyrosine
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A facile and efficient synthesis of N-tert-butoxycarbonyl-O-cyclohexyl-L-tyrosine (Boc-Tyr(Chx)-OH] is described. Boc-Tyr-OH was treated with NaH in dimethylformamide and then with 3-bromocyclohexene to give N-Boc-O-(cyclohex-2-enyl)-L-tyrosine [Boc-Tyr(Che)-OH] in 70% yield. Hydrogenation of Boc-Tyr(Che)-OH over PtO2 afforded Boc-Tyr(Chx)-OH in almost quantitative yield. The highest yield was achieved when a side product in the synthesis of Boc-Tyr-OH, Boc-Tyr(Boc)-OH, was not removed, because it was also converted to Boc-Tyr(Che)-OH without any additional manipulations. The new synthetic method described here is couvenient for practical use, and would facilitate the widespread use of the Chx group for the hydroxy-protection of Tyr.
- Nishiyama,Ishizuka,Shikama,Kurita
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Read Online
- Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite Plasmodium falciparum and Optimization Efforts
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A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure-activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogues followed by whole-genome sequencing implicated the P. falciparum cyclic amine resistance locus in the mode of resistance.
- Le Manach, Claire,Dam, Jean,Woodland, John G.,Kaur, Gurminder,Khonde, Lutete P.,Brunschwig, Christel,Njoroge, Mathew,Wicht, Kathryn J.,Horatscheck, André,Paquet, Tanya,Boyle, Grant A.,Gibhard, Liezl,Taylor, Dale,Lawrence, Nina,Yeo, Tomas,Mok, Sachel,Eastman, Richard T.,Dorjsuren, Dorjbal,Talley, Daniel C.,Guo, Hui,Simeonov, Anton,Reader, Janette,Van Der Watt, Mari?tte,Erlank, Erica,Venter, Nelius,Zawada, Jacek W.,Aswat, Ayesha,Nardini, Luisa,Coetzer, Theresa L.,Lauterbach, Sonja B.,Bezuidenhout, Belinda C.,Theron, Anjo,Mancama, Dalu,Koekemoer, Lizette L.,Birkholtz, Lyn-Marie,Wittlin, Sergio,Delves, Michael,Ottilie, Sabine,Winzeler, Elizabeth A.,Smith, Dennis,Fidock, David A.,Street, Leslie J.,Basarab, Gregory S.,Duffy, James,Chibale, Kelly
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supporting information
p. 2291 - 2309
(2021/03/01)
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- Transition-metal ion-mediated morphological transformation of pyridine-based peptide nanostructures
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Inspired by natural metallopeptides, we have rationally designed two pyridine-conjugated short peptides. These two peptide conjugates formed a pair of constitutional isomers that helped us describe their structure-function relationship. Both the isomers consisted of an equal number of aromatic amino acid residues, but shuffling was observed in the position of two key amino acids, viz; tyrosine and phenylalanine, which brought a remarkable change in their self-assembling behavior. The presence of specific functional groups and chemical diversity in both conjugates made them very active towards metal coordination. Both the constitutional isomers adopted different pathways of self-assembly, which could be further controlled or transformed by the use of transition metal ions. Interestingly, it was observed that the metal ions could precisely control the morphology of these metallopeptide nanostructures and make them more stable. Therefore, such artificial metallopeptides possess remarkable advantages over the natural counterparts primarily due to their tailor-made chemical structures.
- Singh, Narendra,Singh, Ramesh,Sharma, Swati,Kesharwani, Khushboo,Joshi, Khashti Ballabh,Verma, Sandeep
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supporting information
p. 153 - 161
(2021/01/11)
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- Synthesis, in vitro ADME profiling and in vivo pharmacological evaluation of novel glycogen phosphorylase inhibitors
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A small set of indole-2-carboxamide derivatives identified from a high-throughput screening campaign has been described as a novel, potent, and glucose-sensitive inhibitors of glycogen phosphorylase a (GPa). Among this series of compounds, compound 2 exhibited moderate GP inhibitory activity (IC50 = 0.29 μM), good cellular efficacy (IC50 = 3.24 μM for HepG2 cells and IC50 = 7.15 μM for isolated rat hepatocytes), together with good absorption, distribution, metabolism, and elimination (ADME) profiles. The in vivo animal study revealed that compound 2 significantly inhibited an increase of fasting blood glucose level in adrenaline-induced diabetic mice.
- Miao, Guang-xin,Wang, You-de,Yan, Zhi-wei,Zhang, Li-ying
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supporting information
(2020/05/18)
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- Semisynthesis of a Bacterium with Non-canonical Cell-Wall Cross-Links
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The cell wall is an elaborate framework of peptidoglycan that serves to protect the bacterium against osmotic challenge. This exoskeleton is composed of repeating saccharides covalently cross-linked by peptide stems. The general structure of the cell wall is widely conserved across diverse Gram-negative bacteria. To begin to explore the biological consequence of introducing non-canonical cross-links into the cell wall of Escherichia coli, we generated a bacterium where up to 31percent of the cell-wall cross-links are formed by a non-enzymatic reaction between a sulfonyl fluoride and an amino group. Bacteria with these non-canonical cell-wall cross-links achieve a high optical density in culture, divide and elongate successfully, and display no loss of outer membrane integrity. This work represents a first step in the design of bacteria with non-canonical "synthetic"cell walls.
- Chen, Jason S.,Dik, David A.,Schultz, Peter G.,Webb, Bill,Zhang, Nan
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supporting information
p. 10910 - 10913
(2020/07/08)
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- Synthesis of pyrimidine nucleoside and amino acid conjugates
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The synthesis of novel pyrimidine nucleoside bioconjugates with amino acids is presented. The N4-amino acid-acylated 2′-deoxycytidine analogues, modified with various amino acids, were synthesized using a three-step synthesis and obtained in moderate overall yields. Novel amino acid-alkylated 2′-deoxycytidine derivatives were obtained during the rearrangement of amino acid-acylated derivatives that occurred during Boc deprotection.
- Koplūnait?, Martyna,Butkut?, Kamil?,Me?kys, Rolandas,Taurait?, Daiva
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supporting information
(2020/11/13)
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- Total Synthesis of Herquline B and C
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The total syntheses of (-)-herquline B (2) and a heretofore-unrecognized congener, (+)-herquline C (3), are described. The syntheses require 14 and 13 steps, respectively, and feature a key oxazoline reduction that sets the stage for piperazine construction.
- Cox, Joshua B.,Kimishima, Aoi,Wood, John L.
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supporting information
p. 25 - 28
(2019/01/16)
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- α-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease
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Increased Gram-negative bacteria resistance to antibiotics is becoming a global problem, and new classes of antibiotics with novel mechanisms of action are required. The caseinolytic protease subunit P (ClpP) is a serine protease conserved among bacteria that is considered as an interesting drug target. ClpP function is involved in protein turnover and homeostasis, stress response, and virulence among other processes. The focus of this study was to identify new inhibitors of Escherichia coli ClpP and to understand their mode of action. A focused library of serine protease inhibitors based on diaryl phosphonate warheads was tested for ClpP inhibition, and a chemical exploration around the hit compounds was conducted. Altogether, 14 new potent inhibitors of E. coli ClpP were identified. Compounds 85 and 92 emerged as most interesting compounds from this study due to their potency and, respectively, to its moderate but consistent antibacterial properties as well as the favorable cytotoxicity profile.
- Moreno-Cinos, Carlos,Sassetti, Elisa,Salado, Irene G.,Witt, Gesa,Benramdane, Siham,Reinhardt, Laura,Cruz, Cristina D.,Joossens, Jurgen,Van Der Veken, Pieter,Br?tz-Oesterhelt, Heike,Tammela, P?ivi,Winterhalter, Mathias,Gribbon, Philip,Windshügel, Bj?rn,Augustyns, Koen
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p. 774 - 797
(2019/01/30)
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- PREPARATION AND USES OF REACTIVE OXYGEN SPECIES SCAVENGER DERIVATIVES
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Compounds of Formula (I) a or (I) b: including certain quinone derivatives, and the corresponding pharmaceutical compositions, which may serve to modulate ferroptosis in a subject. Also disclosed herein are the preparations of these compounds and pharmaceutical compositions and their potential uses in the manufacture of a medicament in reducing reactive oxygen species (ROS) in a cell and for preventing, treating, ameliorating certain related disorder or a disease.
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Page/Page column 111
(2019/03/07)
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- MRI micelles self-assembled from synthetic gadolinium-based nano building blocks
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A synthetic nano building block endowed with amphiphilic properties and chelated gadolinium is presented. Spontaneous self-assembly into small 12 nm corona-core stealth Gd-micelles with inherently high gadolinium loading occurs in water. Gd-Micelles are a new blood pool contrast agent with high relaxivity for magnetic resonance imaging.
- Babi?, Andrej,Vorobiev, Vassily,Trefalt, Gregor,Crowe, Lindsey A.,Helm, Lothar,Vallée, Jean-Paul,Allémann, Eric
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supporting information
p. 945 - 948
(2019/01/23)
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- Supported Catalytically Active Supramolecular Hydrogels for Continuous Flow Chemistry
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Inspired by biology, one current goal in supramolecular chemistry is to control the emergence of new functionalities arising from the self-assembly of molecules. In particular, some peptides can self-assemble and generate exceptionally catalytically active fibrous networks able to underpin hydrogels. Unfortunately, the mechanical fragility of these materials is incompatible with process developments, relaying this exciting field to academic curiosity. Here, we show that this drawback can be circumvented by enzyme-assisted self-assembly of peptides initiated at the walls of a supporting porous material. We applied this strategy to grow an esterase-like catalytically active supramolecular hydrogel (CASH) in an open-cell polymer foam, filling the whole interior space. Our supported CASH material is highly efficient towards inactivated esters and enables the kinetic resolution of racemates. This hybrid material is robust enough to be used in continuous flow reactors, and is reusable and stable over months.
- Rodon Fores, Jennifer,Criado-Gonzalez, Miryam,Chaumont, Alain,Carvalho, Alain,Blanck, Christian,Schmutz, Marc,Serra, Christophe A.,Boulmedais,Schaaf, Pierre,Jierry, Lo?c
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p. 18817 - 18822
(2019/11/16)
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- Naamine derivatives, preparation method of Nammine derivatives, and application of Nammine derivatives in treatment of plant viruses and bacterial diseases
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The invention discloses Naamine derivatives, a preparation method of the Nammine derivatives, and an application of the Nammine derivatives in treatment of plant viruses and bacterial diseases. The Nammine derivatives specifically are compounds represented as formulae from I-1 to I-16. During each reaction, materials participating in the reaction are taken according to the molar ratio required bythe reaction; excess substances are selected to participate in the reaction so as to ensure the reaction process of a target product; the pH value and reacting temperature and time of a system are determined according to the reaction type; and purifying separation or drying is carried out after the preparation. The Naamine derivatives provided by the invention exhibit good activity for treating plant viruses and bacterial diseases, and can well inhibit the following 14 species of plant pathogenic bacteria: tobacco mosaic virus (TMV), Fusarium oxysporum (Schl.)F.sp cucumerinum Owen, cercosporaarachidicola, Botryospuaeria berengeriana, Rhizotonia cerealis van der Hoeven apud.Boerema & Verhoeven, Helminthosporium maydis Nisik & Miy, Colleetotrichum lagenarium (Pass.) Ell. et Halst, fusariummoniliforme, Alternaria solani, FusaHum graminearum, Phytophthora infestans, phytophthora capsici, sclerotinia sclerotiorum, Botrytis cinerea and Thanatephorus cucumeris.
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Paragraph 0032-0034
(2018/05/16)
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- NOVEL PROCESS FOR THE PREPARATION OF GADOLINIUM COMPLEX OF (4S)-4-(4-ETHOXYBENZYL)-3,6,9-TRIS(CARBOXYLATOMETHYL)-3,6,9- TRIAZAUNDECANEDIOIC ACID DISODIUM (GADOXETATE DISODIUM)
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The present invention discloses a novel process for the preparation of gadolinium complex of (4S)-4-(4-Ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9- triazaundecanedioic acid disodium of formula 1 and novel intermediates thereof.
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Page/Page column 4; 6; 13; 21; 22
(2018/01/17)
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- Asymmetric solution-phase mixture aldol reaction using oligomeric ethylene glycol tagged chiral oxazolidinones
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Sorting tags are oligomeric structures that can be used as protecting groups or chiral auxiliaries enabling solution-phase mixture syntheses of multiple tagged compounds in one pot and allowing for facile and predictable chromatographic separation of products at the end of synthetic sequences. Perfluorinated hydrocarbon and oligomeric ethylene glycol (OEG) derivatives are known classes of sorting tags. Herein we describe the preparation of OEGylated chiral oxazolidinones and their use in asymmetric solution-phase mixture aldol reactions. Through the use of such oxazolidinones based on tyrosine four different individually tagged aldol adducts were obtained as a mixture, chromatographically demixed, detagged, and it was shown that these processes gave the desired aldol products in good yield and enantioselectivity.
- Turkyilmaz, Serhan,Wilcox, Craig S.
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supporting information
p. 2031 - 2033
(2017/05/04)
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- Design, Synthesis, and Evaluation of Novel Tyrosine-Based DNA Gyrase B Inhibitors
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The discovery and synthesis of new tyrosine-based inhibitors of DNA gyrase B (GyrB), which target its ATPase subunit, is reported. Twenty-four compounds were synthesized and evaluated for activity against DNA gyrase and DNA topoisomerase IV. The antibacterial properties of selected GyrB inhibitors were demonstrated by their activity against Staphylococcus aureus and Enterococcus faecalis in the low micromolar range. The most promising compounds, 8a and 13e, inhibited Escherichia coli and S. aureus GyrB with IC50 values of 40 and 30 μM. The same compound also inhibited the growth of S. aureus and E. faecalis with minimal inhibitory concentrations (MIC90) of 14 and 28 μg/mL, respectively.
- Cotman, Andrej E.,Trampu?, Marko,Brvar, Matja?,Kikelj, Danijel,Ila?, Janez,Peterlin-Ma?i?, Lucija,Montalv?o, Sofia,Tammela, P?ivi,Frlan, Rok
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- Chiral enantiopure organosilane precursors for the synthesis of periodic mesoporous organosilicas
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The manuscript describes synthesis of new chiral organosilica networks starting from modified readily available enantiopure substances such as sugars and amino acids. We report on the successful preparation of robust all-chiral organosilicas by polymerization of the homochiral monomers. When the homochiral organosilane monomers were polymerized in mixtures of polar organic solvents and water in the presence of hydrochloric acid or tetrabutylammonium fluoride as catalysts, mainly spherical microparticles were obtained due to emulsification of the hydrophobic monomers in these mixtures. Polycondensation of the chiral organosilanes in the presence of Pluronic P123 as a template produced ordered mesoporous networks. The new all-chiral materials were characterized by SEM, STEM, BET, SAXS, IR, NMR and TGA.
- Cohen, Orit,Abu-Reziq, Raed,Gelman, Dmitri
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p. 1675 - 1685
(2017/11/17)
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- Photoinduced electron transfer-promoted debenzylation of phenylalanine and tyrosine derivatives using dicyanoarene
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Photoinduced debenzylations of phenylalanine and tyrosine derivatives with dicyanoarenes afford glycine derivatives by the generation of radical cations. Despite the limited substrate scope, the radical cation of phenylalanine and tyrosine derivatives bearing both a carbamate (without an aromatic group) at the N-terminal and an amide at the C-terminal could promote the breaking C–C bond at the benzylic position by a photoinduced electron transfer. It is important to understand the chemical behavior of the radical cations of phenylalanine and tyrosine in enzymes involving electron transfer.
- Yamawaki, Mugen,Okita, Yoshiki,Yamamoto, Takashi,Morita, Toshio,Yoshimi, Yasuharu
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p. 7239 - 7244
(2017/11/20)
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- 4-oxo-alkylated tetramic acid compounds and preparation method thereof
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The invention relates to novel compounds and a preparation method thereof. The general structural formula is shown as formula I in the description. Animal experiments prove that the compounds have the effect of saving memories of animal models, are high in safety, have no mutagenicity, can remain in blood for hours after oral administration and intravenous injection, can enter brains and can be used for preparing drugs for treating diseases such as Alzihemer's disease, Parkinson's disease, Huntington's disease, vascular dementia, schizophrenia, autism and the like.
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Paragraph 0169; 0170
(2017/12/09)
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- 4-oxo-alkylated tetramic acid compound as well as preparation method and application thereof
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The invention relates to a novel compound as well as preparation method and application thereof. The structural formula of the novel compound is as shown in a formula I. Animal tests show that the compound provided by the invention has a memory effect of rescuing animal models, is high in security and free of mutagenicity induction, can be retained for hours in blood after oral taking and intravenous injection, can be fed into brains and can be used for preparing medicines for treating senile dementia, Parkinsonism, Huntington diseases, vascular dementia, schizophrenia, autism and the like.
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Paragraph 0169; 0170
(2018/01/09)
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- New reagent for the introduction of Boc protecting group to amines: Boc-OASUD
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A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.
- Maheswara Rao, B. Leela,Nowshuddin, Shaik,Jha, Anjali,Divi, Murali K.,Rao
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supporting information
p. 2127 - 2132
(2017/10/31)
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- Reagent Design and Ligand Evolution for the Development of a Mild Copper-Catalyzed Hydroxylation Reaction
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Parallel synthesis and mass-directed purification of a modular ligand library, high-throughput experimentation, and rational ligand evolution have led to a novel copper catalyst for the synthesis of phenols with a traceless hydroxide surrogate. The mild reaction conditions reported here enable the late-stage synthesis of numerous complex, druglike phenols.
- Fier, Patrick S.,Maloney, Kevin M.
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supporting information
p. 3033 - 3036
(2017/06/07)
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- Synthesis of Met-enkephalin by solution-phase peptide synthesis methodology utilizing para-toluene sulfonic acid as N-terminal masking of l-methionine amino acid
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The Met-enkephalin, Tyr-Gly-Gly-Phe-Met, was synthesized by the solution-phase synthesis (SPS) methodology employing -OBzl group as carboxyls' protection, while the t-Boc groups were employed for the N-terminal α-amines' protection for the majority of the amino acids of the pentapeptide sequence. The l-methionine (l-Met) amino acid was used as PTSA.Met-OBzl obtained from the simultaneous protection of the α-amino, and carboxyl group with para-toluene sulfonic acid (PTSA) and as-OBzl ester, respectively in a C-terminal start of the 2?+?2?+?1 fragments condensation convergent synthetic approach. The protection strategy provided a short, single-step, simultaneous, orthogonal, nearly quantitative, robust, and stable process to carry through the protected l-methionine and l-phenylalanine coupling without any structural deformities during coupling and workups. The structurally confirmed final pentapeptide product was feasibly obtained in good yields through the current approach.
- Khan, Riaz A.
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p. 884 - 888
(2016/11/11)
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- Design, synthesis, and in vitro and biological evaluation of potent amino acid-derived thiol inhibitors of the metallo-β-lactamase IMP-1
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There are currently no clinically available inhibitors of metallo-β-lactamases (MBLs). These enzymes confer resistance to bacteria against a broad range of commonly used β-lactam antibiotics, and are produced by an increasing number of bacterial pathogens. In this study, several thiol derivatives of l-amino acids were designed and synthesized, and their inhibitory effects against the metallo-β-lactamase IMP-1 (subclass B1) were investigated. The most potent compound, derived from l-tyrosine, exhibited competitive inhibition, with a Ki of 86 nM. The ability of this compound to render MBL-expressing bacteria susceptible to imipenem was examined. Reductions in MIC values up to 5.2 - fold were observed.
- Arjomandi, Omid Khalili,Hussein, Waleed M.,Vella, Peter,Yusof, Yusralina,Sidjabat, Hanna E.,Schenk, Gerhard,McGeary, Ross P.
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p. 318 - 327
(2016/04/05)
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- Tyrosine-Based Ionic Liquid Crystals: Switching from a Smectic A to a Columnar Mesophase by Exchange of the Spherical Counterion
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Synthetic strategies were developed to prepare l-tyrosine-based ionic liquid crystals with structural variations at the carboxylic and phenolic OH groups as well as the amino functionality. Salt metathesis additionally led to counterion variation. The liquid-crystalline properties were investigated by differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction (WAXS, SAXS). The symmetrical ILC chlorides bearing the same alkyl chain at both the ester and ether but either an acyclic or cyclic guanidinium group displayed enantiotropic SmA2mesophases with phase widths of 31–88 K irrespective of the head group. It was particularly the replacement of chloride in the acyclic guanidinium ILC by hexafluorophosphate that induced a phase change from SmA2to Colr. This phase change was attributed to a higher curvature of the interface due to the larger anion, which increased the effective head group cross-sectional area of the amphiphilic ILC. The unsymmetrical acyclic guanidinium chlorides, bearing a constant C14ester and variable alkyl chains on the phenolic position, formed enantiotropic SmA2phases. The derivative with the largest difference in chain lengths, however, displayed a Colrphase, resulting from discoid aggregates of the cone-shaped guanidinium chloride. The results are discussed in terms of the packing parameters, which indicate that the phase behaviour of the thermotropic tyrosine-based ILCs shows analogies to those of lyotropic liquid crystals.
- Neidhardt, Manuel M.,Wolfrum, Manpreet,Beardsworth, Stuart,W?hrle, Tobias,Frey, Wolfgang,Baro, Angelika,Stubenrauch, Cosima,Giesselmann, Frank,Laschat, Sabine
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supporting information
p. 16494 - 16504
(2016/11/09)
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- Synthesis and Antibacterial Activity of Four Stereoisomers of the Spider-Pathogenic Fungus Metabolite Torrubiellone D
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Four stereoisomers of the spider-pathogenic fungus metabolite torrubiellone D were synthesized for the first time in 10% overall yield starting from l-tyrosine or d-tyrosine. The 3-decatrienoyl side chain was assembled and attached via (E)-selective HWE and Wittig olefinations. Their antibiotic activities against drug-susceptible Escherichia coli strains differed considerably.
- Bruckner, Sebastian,Bilitewski, Ursula,Schobert, Rainer
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supporting information
p. 1136 - 1139
(2016/03/15)
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- Photochemical formation of quinone methides from peptides containing modified tyrosine
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We have demonstrated that quinone methide (QM) precursors can be introduced in the peptide structure and used as photoswitchable units for peptide modifications. QM precursor 1 was prepared from protected tyrosine in the Mannich reaction, and further used as a building block in peptide synthesis. Moreover, peptides containing tyrosine can be transformed into a photoactivable QM precursor by the Mannich reaction which can afford monosubstituted derivatives 2 or bis-substituted derivatives 3. Photochemical reactivity of modified tyrosine 1 and dipeptides 2 and 3 was studied by preparative irradiation in CH3OH where photodeamination and photomethanolysis occur. QM precursors incorporated in peptides undergo photomethanolysis with quantum efficiency ΦR = 0.1-0.2, wherein the peptide backbone does not affect their photochemical reactivity. QMs formed from dipeptides were detected by laser flash photolysis (λmax ≈ 400 nm, τ = 100 μs-20 ms) and their reactivity with nucleophiles was studied. Consequently, QM precursors derived from tyrosine can be a part of the peptide backbone which can be transformed into QMs upon electronic excitation, leading to the reactions of peptides with different reagents. This proof of principle showing the ability to photochemically trigger peptide modifications and interactions with other molecules can have numerous applications in organic synthesis, materials science, biology and medicine.
- Husak, Antonija,Noichl, Benjamin P.,?umanovac Ramljak, Tatjana,Sohora, Margareta,?kalamera,Budi?a, Nediljko,Basari?, Nikola
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supporting information
p. 10894 - 10905
(2016/12/06)
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- Sulfotyrosine dipeptide: Synthesis and evaluation as HIV-entry inhibitor
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Human immunodeficiency virus type 1 (HIV-1) is responsible for the worldwide AIDS pandemic. Due to the lack of prophylactic HIV-1 vaccine, drug treatment of the infected patients becomes essential to reduce the viral load and to slow down progression of the disease. Because of drug resistance, finding new antiviral agents is necessary for AIDS drug therapies. The interaction of gp120 and co-receptor (CCR5/CXCR4) mediates the entry of HIV-1 into host cells, which has been increasingly exploited in recent years as the target for new antiviral agents. A conserved co-receptor binding site on gp120 that recognizes sulfotyrosine (sTyr) residues represents a structural target to design novel HIV entry inhibitors. In this work, we developed an efficient synthesis of sulfotyrosine dipeptide and evaluated it as an HIV-1 entry inhibitor.
- Ju, Tong,Hu, Duoyi,Xiang, Shi-Hua,Guo, Jiantao
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p. 105 - 111
(2016/08/02)
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- Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates
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Abstract: A new series of side chain-modified 4-aminoquinolines were synthesized and screened for in vitro antiplasmodial activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Among the series, compounds 30 and 31 showed significant inhibition of parasite growth against K1 strain of P. falciparum with IC50 values 0.28 and 0.31?μM, respectively, whereas compounds 34, 35, and 38 exhibited superior activity against K1 strain with IC50 values 0.18, 0.22, and 0.17?μM, respectively, as compared to 0.255?μM for chloroquine (CQ). All the compounds displayed good resistance factor between 1.54 and >34.48 as against 51.0 for CQ. All these analogues were found to form strong complex with hematin and inhibited the β-hematin formation in vitro, suggesting that this class of compounds act on a heme polymerization target. Overall results suggest that present series of compounds appear to be promising for further lead optimization to obtain compounds active against drug-resistant parasites. Graphical Abstract: [Figure not available: see fulltext.]
- Srinivasarao, Kondaparla,Agarwal, Pooja,Srivastava, Kumkum,Haq,Puri, Sunil K.,Katti
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p. 1148 - 1162
(2016/07/06)
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- Facile Removal of Leader Peptides from Lanthipeptides by Incorporation of a Hydroxy Acid
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The biosynthesis of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products typically involves a precursor peptide which contains a leader peptide that is important for the modification process, and that is removed in the final step by a protease. Genome mining efforts for new RiPPs are often hampered by the lack of a general method to remove the leader peptides. We describe here the incorporation of hydroxy acids into the precursor peptides in E. coli which results in connection of the leader peptide via an ester linkage that is readily cleaved by simple hydrolysis. We demonstrate the method for two lantibiotics, lacticin 481 and nukacin ISK-1.
- Bindman, Noah A.,Bobeica, Silvia C.,Liu, Wenshe R.,Van Der Donk, Wilfred A.
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supporting information
p. 6975 - 6978
(2015/06/25)
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- Synthesis of Chiral Polyethers Containing Imidazolidinone Repeating Units and Application as Catalyst in Asymmetric Diels-Alder Reaction
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In this study, enantiopure imidazolidinones containing two hydroxyphenyl groups were synthesized, and the Williamson synthesis of the chiral bisphenols thus prepared with dihalides afforded polyethers containing chiral imidazolidinone repeating units. These chiral imidazolidinone polyethers exhibited excellent catalytic activity in the asymmetric Diels-Alder reaction. With the use of these polymeric catalysts, enantioselectivities up to 99% were obtained, higher than those obtained by the corresponding monomeric imidazolidinone catalyst in homogeneous solution. The polymeric catalysts were found to be insoluble in commonly used organic solvents, and they could be repeatedly used without the loss of activity.
- Itsuno, Shinichi,Oonami, Tatsuaki,Takenaka, Nagisa,Haraguchi, Naoki
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supporting information
p. 3995 - 4002
(2016/01/25)
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- Versatile and Efficient Site-Specific Protein Functionalization by Tubulin Tyrosine Ligase
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A novel chemoenzymatic approach for simple and fast site-specific protein labeling is reported. Recombinant tubulin tyrosine ligase (TTL) was repurposed to attach various unnatural tyrosine derivatives as small bioorthogonal handles to proteins containing a short tubulin-derived recognition sequence (Tub-tag). This novel strategy enables a broad range of high-yielding and fast chemoselective C-terminal protein modifications on isolated proteins or in cell lysates for applications in biochemistry, cell biology, and beyond, as demonstrated by the site-specific labeling of nanobodies, GFP, and ubiquitin.
- Schumacher, Dominik,Helma, Jonas,Mann, Florian A.,Pichler, Garwin,Natale, Francesco,Krause, Eberhard,Cardoso, M. Cristina,Hackenberger, Christian P. R.,Leonhardt, Heinrich
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supporting information
p. 13787 - 13791
(2015/11/10)
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- Synthesis and antibacterial activity of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate
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A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate discovered in our lab, were synthesized and evaluated for their water solubility and then antibacterial activity. Our results reveal that four amino acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have much greater solubility (>85 mg/mL) than IMB-070593 mesylate (22.5 mg/mL). Compounds 4a and 4k show good in vivo efficacy against MSSA 12-1 (p.o./i.v., 5.32-7.68 mg/kg) and S. pneumoniae12-10 (p.o., 18.39-23.13 mg/kg) which is 1.19-1.50 fold more active than the parent drug.
- Zhang, Tingting,Wu, Jinwei,Chen, Shihong,Liu, Kaixiang,Lin, Yabin,Guo, Huiyuan,Liu, Mingliang
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p. 6822 - 6837
(2014/06/10)
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- Quantitative insight into the design of compounds recognized by the L-type amino acid transporter 1 (LAT1)
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L-Type amino acid transporter 1 (LAT1) is a transmembrane protein expressed abundantly at the blood-brain barrier (BBB), where it ensures the transport of hydrophobic acids from the blood to the brain. Due to its unique substrate specificity and high expression at the BBB, LAT1 is an intriguing target for carrier- mediated transport of drugs into the brain. In this study, a comparative molecular field analysis (CoMFA) model with considerable statistical quality (Q2=0.53, R2=0.75, Q2 SE=0.77, R2 SE=0.57) and good external predictivity (CCC=0.91) was generated. The model was used to guide the synthesis of eight new prodrugs whose affinity for LAT1 was tested by using an in situ rat brain perfusion technique. This resulted in the creation of a novel LAT1 prodrug with l-tryptophan as the promoiety; it also provided a better understanding of the molecular features of LAT1-targeted high-affinity prodrugs, as well as their promoiety and parent drug. The results obtained will be beneficial in the rational design of novel LAT1-binding prodrugs and other compounds that bind to LAT1.
- Ylikangas, Henna,Malmioja, Kalle,Peura, Lauri,Gynther, Mikko,Nwachukwu, Emmanuel O.,Lepp?nen, Jukka,Laine, Krista,Rautio, Jarkko,Lahtela-Kakkonen, Maija,Huttunen, Kristiina M.,Poso, Antti
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supporting information
p. 2699 - 2707
(2015/02/02)
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- Synthesis of new DOPA derivative from l-tyrosine for construction of bioactive compound
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A practical synthetic method of new DOPA derivative was developed with L-tyrosine as starting material. The new DOPA analogue could be used in building bioactive compounds.
- Sun, Dequn,Wan, Peihong,Zhang, Guoqing,Luo, Min
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p. 9407 - 9408
(2013/11/19)
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- Design, synthesis and biological evaluation of novel L-isoserine tripeptide derivatives as aminopeptidase N inhibitors
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Aminopeptidase N (APN/CD13) is one of the essential proteins for tumour invasion, angiogenesis and metastasis as it is over-expressed on the surface of different tumour cells. Based on our previous work that L-isoserine dipeptide derivatives were potent APN inhibitors, we designed and synthesized L-isoserine tripeptide derivatives as APN inhibitors. Among these compounds, one compound 16l (IC50=2.51±0.2 M) showed similar inhibitory effect compared with control compound Bestatin (IC50=6.25±0.4 M) and it could be used as novel lead compound for the APN inhibitors development as anticancer agents in the future.
- Pan, Huili,Yang, Kanghui,Zhang, Jian,Xu, Yingying,Jiang, Yuqi,Yuan, Yumei,Zhang, Xiaopan,Xu, Wenfang
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p. 717 - 726
(2013/07/26)
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- A rationally designed pyrrolysyl-tRNA synthetase mutant with a broad substrate spectrum
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Together with tRNACUAPyl, a rationally designed pyrrolysyl-tRNA synthetase mutant N346A/C348A has been successfully used for the genetic incorporation of a variety of phenylalanine derivatives with large para substituents into superfolder green fluorescent protein at an amber mutation site in Escherichia coli. This discovery greatly expands the genetically encoded noncanonical amino acid inventory and opens the gate for the genetic incorporation of other phenylalanine derivatives using engineered pyrrolysyl-tRNA synthetase-tRNACUAPyl pairs.
- Wang, Yane-Shih,Fang, Xinqiang,Wallace, Ashley L.,Wu, Bo,Liu, Wenshe R.
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supporting information; experimental part
p. 2950 - 2953
(2012/04/10)
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- Dynamic interface imprinting: High-affinity peptide binding sites assembled by analyte-induced recruiting of membrane receptors
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Come together: Dynamic molecular recognition events at biological membrane receptors play a key role in cell signaling. Artificial membranes have been prepared with embedded synthetic receptors which dynamically arrange and selectively respond to external stimuli, such as, small peptide ligands. Copyright
- Gruber, Benjamin,Balk, Stefan,Stadlbauer, Stefan,Koenig, Burkhard
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supporting information
p. 10060 - 10063,4
(2012/12/12)
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- Dynamic interface imprinting: High-affinity peptide binding sites assembled by analyte-induced recruiting of membrane receptors
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Come together: Dynamic molecular recognition events at biological membrane receptors play a key role in cell signaling. Artificial membranes have been prepared with embedded synthetic receptors which dynamically arrange and selectively respond to external stimuli, such as, small peptide ligands. Copyright
- Gruber, Benjamin,Balk, Stefan,Stadlbauer, Stefan,K?nig, Burkhard
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supporting information
p. 10060 - 10063
(2013/01/15)
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- Poly(vinyl)chloride supported palladium nanoparticles: Catalyst for rapid hydrogenation reactions
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Palladium nanoparticles supported over poly(vinyl)chloride matrix (PVC-Pd0) are prepared through an efficient and inexpensive protocol. The catalyst has been characterized by XRD, SEM and TEM and its utility for the reduction of a range of functional groups as well as for the removal of some common protecting groups employed in peptide chemistry is demonstrated.
- Hemantha, Hosahalli P.,Sureshbabu, Vommina V.
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experimental part
p. 2597 - 2601
(2011/05/12)
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- A new peptide motif in the formation of supramolecular double helices
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The single crystal X-ray diffraction studies of a new tripeptide motif Boc-Tyr-Aib-Xaa-OMe (Xaa = Leu/Ile/Ala) reveal that the peptides adopt β-turn conformations which self-assemble to form a supramolecular double helical structure using various non-covalent interactions in the solid state and the peptides exhibit a type-III N2 sorption isotherm.
- Jana, Poulami,Maity, Sibaprasad,Maity, Suman Kumar,Haldar, Debasish
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supporting information; experimental part
p. 2092 - 2094
(2011/04/14)
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- Insights into self-assembling nanoporous peptide and in situ reducing agent
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A tripeptide containing an Aib (α-amino isobutyric acid) residue self-assembles to form porous nanomaterials in solid state. In spite of having a hollow nanotubular structure, the self-assembly nature of the peptide is different, which leads to the formation of pores with different internal diameters. The single-crystal X-ray diffraction study reveals that the peptide forms continuous hydrogen-bonded poly-disperse nanopores (3, 5 and 8 membered) starting from the β-turn conformation as an associating sub-unit. The field emission scanning electron micrograph (FESEM) shows that the average pore sizes are in the range of 20 to 200 nm, although a few large pores are also visible. Moreover, the peptide 1 acts as an in situ reducing agent to synthesize hexagonal gold nanoparticles (GNP).
- Jana, Poulami,Maity, Sibaprasad,Haldar, Debasish
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experimental part
p. 973 - 978
(2012/02/01)
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- Design, synthesis and primary activity assay of tripeptidomimetics as histone deacetylase inhibitors with linear linker and branched cap group
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A novel series of tripeptidomimetics with spiro ring containing sulfur atoms as cap group and linear carbochain as linker was designed and synthesized as HDACs inhibitors. Several compounds possessed more potent HDAC8 inhibitory activity than clinically used drug SAHA, although their HDAC1 inhibitory activities and anti-proliferative activities against human breast cancer cell lines (MCF-7, MDA-MB-231) and prostate cancer cell line (PC-3) were not satisfactory. Among them, compounds 11l and 11k showed excellent potency against HDAC8 (IC50 values were 0.021 ± 0.004 μM and 0.035 ± 0.007 μM, respectively, whereas SAHA was 0.70 ± 0.12 μM), and good selectivity over HDAC1. Up to now, few hydroxamic acid derivatives with linear linker were reported to possess HDAC8 selectivity over HDAC1.
- Zhang, Yingjie,Feng, Jinhong,Jia, Yuping,Xu, Yingying,Liu, Chunxi,Fang, Hao,Xu, Wenfang
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experimental part
p. 5387 - 5397
(2011/12/14)
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- Design, synthesis and biological evaluation of tyrosine-based hydroxamic acid analogs as novel histone deacetylases (HDACs) inhibitors
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Histone deacetylases (HDACs) are a promising target for treating cancer and some other disorders. Herein, based on the structure of our previously reported tetrahydroisoquinoline-based hydroxamic acids, a novel series of tyrosine-based hydroxamic acid derivatives was designed and synthesized as HDACs inhibitors. Compared with tetrahydroisoquinoline-based hydroxamic acids, tyrosine-based hydroxamic acid derivatives exhibited more potent HDAC8 inhibitory activity. However, the antiproliferative activities and HeLa cell nuclear extract inhibition of several selected tyrosine-based hydroxamic acids were moderate.
- Zhang, Yingjie,Feng, Jinhong,Liu, Chunxi,Fang, Hao,Xu, Wenfang
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experimental part
p. 4437 - 4444
(2012/04/23)
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- THIOCOLCHICINE DERIVATIVES, METHOD OF MAKING AND METHODS OF USE THEREOF
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Disclosed herein are thiocolchicine derivatives suitable for use as muscle relaxants, methods of making the derivatives, and compositions comprising the derivatives.
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Page/Page column 23-24
(2010/12/26)
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- Peptide-based activity-based probes (ABPs) for target-specific profiling of protein tyrosine phosphatases (PTPs)
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Synthesis of a novel unnatural amino acid (2-FMPT) for the solid-phase synthesis of peptide-based probes suitable for target-specific activity-based profiling of protein tyrosine phosphatases from crude proteomes is reported.
- Kalesh, Karunakaran A.,Tan, Lay Pheng,Lu, Kai,Gao, Liqian,Wang, Jigang,Yao, Shao Q.
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supporting information; experimental part
p. 589 - 591
(2010/05/01)
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- Construction of the cyclophane core of the hirsutellones via a RCM strategy
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Construction of the highly strained [10]-paracyclophane core of the hirsutellones has been completed via an effective RCM strategy.
- Huang, Mingzheng,Song, Liqiang,Liu, Bo
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supporting information; experimental part
p. 2504 - 2507
(2010/07/05)
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- Mapping the sirodesmin PL biosynthetic pathway- A remarkable intrinsic steric deuterium isotope effect on a 1H NMR chemical shift determines β-proton exchange in tyrosine
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Sirodesmin PL is both an antibiotic and a phytotoxin produced by a fungal plant pathogen (Leptosphaeria maculans,asexual stage Phoma lingam) that causes blackleg disease on crucifers. To determine potential biosynthetic precursors of sirodesmin PL, deuterated compounds were synthesized and incubated with cultures of L. maculans. Incorporations of deuterium into sirodesmin PL (7) and its precursor phomamide (4) were determined using 1H and 13C NMR spectroscopy, LCHRMS-ESI and HRMS-EI spectrometry. Spectroscopic analyses established that [3,3-2H2]L- tyrosine (1a), [3,3-2H2]O-prenyl-L-tyrosine (9a), [3,3,5',5',5'-2H5]O-prenyl-L-tyrosine (9b), and [5,5- 2H2]phomamide (4a) were incorporated efficiently into sirodesmin PL (7). Interestingly, an unexpected "twist" revealed that one of the β-deuteria (pro-R) of [3,3-2H2]L-tyrosine (1a) was exchanged stereospecifically before incorporation into sirodesmin PL (7). As well, our studies revealed that O-prenyl-Ltyrosine is likely to be the first committed precursor en route to sirodesmin PL (7).
- Pedras, M. Soledade C.,Yu, Yang
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supporting information; scheme or table
p. 556 - 562
(2009/10/17)
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- Asymmetric syntheses and Wnt signal inhibitory activity of melleumin A and four analogues of melleumins A and B
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The first total synthesis of melleumin A and four analogues of melleumins A and B is described. The N-acyl L-Thr-Gly/β-hydroxy-γ-amino acid coupling/macrolactamization strategy allowed the efficient assembly of the three segments being free of epimerization. While the Jouin-Castro method with minor modification allows a rapid entrance to the key syn-β-hy-droxy-y-amino acid segment, required for the synthesis of melleumin A, an extension of our malimide-based methodology using a changed N-protecting group affords a flexible access to several anti-β-hydroxy-γ-amino acids, and hence analogues of melleumins A and B. Among them, unnatural 4-epi-melleumin B (2a) exhibits a modest inhibitory activity on Wnt signaling. The total synthesis of melleumin A allowed confirmation of its full structure.
- Luo, Jie-Min,Dai, Chao-Feng,Lin, Shu-Yong,Huang, Pei-Qiang
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supporting information; experimental part
p. 328 - 335
(2010/04/23)
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- Chiral tetraazamacrocycles having four pendant-arms
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A chiral tetraazamacrocycle 9 having four pendant-arms was synthesized by repeating ring opening of an Ns-aziridine with secondary amines, followed by macrocyclization. The structure of 9 has been determined by single crystal X-ray diffraction analysis and NMR studies. Sugarhybrid molecules 12a-12f were synthesized based on the scaffold 9. NMR study showed that 12a-12f keep the similar conformation as 9 in solution.
- Kamioka, Seiji,Takahashi, Takashi,Kawauchi, Susumu,Adachi, Hiroaki,Mori, Yusuke,Fujii, Kotaro,Uekusa, Hidehiro,Doi, Takayuki
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supporting information; experimental part
p. 2289 - 2292
(2009/10/02)
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- Ditryptophan conjugation triggers conversion of biotin fibers into soft spherical structures
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(Figure Presented) Trigger happy: Biotin and its methyl ester form long fibers in solution, which are transformed into soft spherical structures upon simple conjugation with ditryptophan dipeptide (see picture). Such morphogenesis is not achieved in a controlled fashion by other aromatic amino acids.
- Joshi,Verma, Sandeep
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supporting information; experimental part
p. 2860 - 2863
(2009/02/06)
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- Novel Dipeptides incorporating selenoamino acids with enhanced bioavailability- Synthesis, pharmaceutical and cosmeceutical applications thereof
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Disclosed is a novel synthetic method for isomeric peptides through an appropriate linkage of L-selenomethionine or Se-Methyl-L-selenocysteine with L-glutamic acid. The novel synthetic method produces isomeric peptides of L-selenomethionine or Se-Methyl-L-selenocysteine that exhibit (i) enhanced water solubility; (ii) enhanced rate of dissolution in water; (iii) enhanced bioavailability; (iv) excellent vascular endothelial growth factor promoting activity; (v) excellent anti-5-alpha-reductase activity; (vi) capabilities to prevent/reduce “hair fall” and promote “hair growth”, thereby maintaining a perfect homeostasis for “hair care”. Cosmeceutical and pharmaceutical compositions comprising the isomeric peptides obtained through an appropriate linkage of L-selenomethionine or Se-Methyl-L-selenocysteine with L-glutamic acid are also disclosed. Other dipeptides with several other amino acids and uses thereof are also disclosed.
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Page/Page column 13
(2010/11/29)
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