- Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and in Vivo Biological Evaluation for Acute Lung Injury
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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a nat
- Cui, Yingjun,Zhang, Mengyi,Xu, Honglei,Zhang, Tingrong,Zhang, Songming,Zhao, Xiuhe,Jiang, Peng,Li, Jing,Ye, Baijun,Sun, Yuanjun,Wang, Mukuo,Deng, Yangping,Meng, Qing,Liu, Yang,Fu, Qiang,Lin, Jianping,Wang, Liang,Chen, Yue
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p. 2971 - 2987
(2022/01/27)
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- Peptidotriazolamers Inhibit Aβ(1–42) Oligomerization and Cross a Blood-Brain-Barrier Model
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In peptidotriazolamers every second peptide bond is replaced by a 1H-1,2,3-triazole. Such foldamers are expected to bridge the gap in molecular weight between small-molecule drugs and protein-based drugs. Amyloid β (Aβ) aggregates play an important role in Alzheimer's disease. We studied the impact of amide bond replacements by 1,4-disubstituted 1H-1,2,3-triazoles on the inhibitory activity of the aggregation “hot spots” K16LVFF20 and G39VVIA42 in Aβ(1–42). We found that peptidotriazolamers act as modulators of the Aβ(1–42) oligomerization. Some peptidotriazolamers are able to interfere with the formation of toxic early Aβ oligomers, depending on the position of the triazoles, which is also supported by computational studies. Preliminary in vitro results demonstrate that a highly active peptidotriazolamer is also able to cross the blood-brain-barrier.
- Tonali, Nicolo,Hericks, Loreen,Schr?der, David C.,Kracker, Oliver,Krzemieniecki, Rados?aw,Kaffy, Julia,Le Joncour, Vadim,Laakkonen, Pirjo,Marion, Antoine,Ongeri, Sandrine,Dodero, Veronica I.,Sewald, Norbert
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p. 840 - 851
(2021/05/05)
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- Small molecule peptidomimetic trypsin inhibitors: validation of an EKO binding mode, but with a twist
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Examination of a series of naturally-occurring trypsin inhibitor proteins, led to identification of a set of three residues (which we call the “interface triplet”) to be determinant of trypsin binding affinity, hence excellent templates for small molecule mimicry. Consequently, we attempted to use the Exploring Key Orientation (EKO) strategy developed in our lab to evaluate small molecules that mimic the interface triplet regions of natural trypsin inhibitors, and hence potentially might bind and inhibit the catalytic activity of trypsin. A bis-triazole scaffold (“TT-mer”) was the most promising of the molecules evaluated in silico. Twelve such compounds were synthesized and assayed against trypsin, among which the best showed a Kd of 2.1 μM. X-ray crystallography revealed a high degree of matching between an illustrative TT-mer's actual binding mode and that of the mimics that overlaid the interface triplet in the crystal structure. Deviation of the third side chain from the PPI structure seems to be due to alleviation of an unfavorable dipole-dipole interaction in the small molecule's actual bound conformation.
- Burgess, Kevin,Joy, Shaon,Laganowsky, Arthur,Lyu, Rui-Liang,Packianathan, Charles
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supporting information
p. 2075 - 2080
(2022/03/31)
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- Synthesis and biological activity evaluation of dolastatin 10 analogues with N-terminal modifications
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We have described the synthesis of the two complex units (2R,3R,4S)-dolaproine (Dap) and (3R,4S,5S)-dolaisoleuine (Dil) of dolastatin 10 from natural amino acids. The stereoselective syntheses of N-Boc-Dap (4a) and N-Boc-(2S)-iso-Dap (4b) were performed by employing crotylation of N-Boc-L-prolinal as a key step. Barbier-type allylation of N-Boc-L-isoleucinal provided a mild and convenient approach for the synthesis of N-Boc-Dil (5a) and N-Boc-(3S)-iso-Dil (5b). Ten dolastatin 10 analogues have been designed and synthesized with N-terminal modifications based on the known compound monomethylauristatin F (MMAF, 3). In comparison with MMAF (3), four of the compounds showed enhanced potency against HCT 116 human colon cancer cells in?vitro.
- Wang, Xin,Dong, Suzhen,Feng, Dengke,Chen, Yazhou,Ma, Mingliang,Hu, Wenhao
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p. 2255 - 2266
(2017/03/24)
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- Synthesis, SAR and biological studies of sugar amino acid-based almiramide analogues: N-methylation leads the way
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Leishmaniasis, caused by the protozoan parasites of the genus Leishmania, is one of the most neglected diseases endemic in many continents posing enormous global health threats and therefore the discovery of new antileishmanial compounds is of utmost urgency. The antileishmanial activities of a library of sugar amino acid-based linear lipopeptide analogues were examined with the aim to identify potential drug candidates to treat visceral leishmaniasis. It was found that among the synthesized analogues, most of the permethylated compounds exhibited more activity in in vitro studies against intra-macrophagic amastigotes than the non-methylated analogues. SAR and NMR studies revealed that introduction of the N-methyl groups inhibited the formation of any turn structure in these molecules, which led to their improved activities.
- Das, Dipendu,Khan, Hina P. A.,Shivahare, Rahul,Gupta, Suman,Sarkar, Jayanta,Siddiqui, Mohd. Imran,Ampapathi, Ravi Sankar,Chakraborty, Tushar Kanti
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p. 3337 - 3352
(2017/04/21)
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- Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics
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The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4-substituted 1,2,3-triazole moieties. The introduction of non-peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non-natural triazole-containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation.
- Oueis, Emilia,Jaspars, Marcel,Westwood, Nicholas J.,Naismith, James H.
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supporting information
p. 5842 - 5845
(2016/05/09)
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- Chemo- and Diastereoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions Using N-Boc-α-amino Aldehydes
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N-Boc-α-amino aldehydes are shown to be excellent partners in cross-benzoin reactions with aliphatic or heteroaromatic aldehydes. The chemoselectivity of the reaction and the facial selectivity on the amino aldehyde allow cross-benzoin products to be obtained in good yields and good diastereomeric ratios. The developed method is utilized as the key step in a concise total synthesis of d-arabino-phytosphingosine.
- Haghshenas, Pouyan,Gravel, Michel
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supporting information
p. 4518 - 4521
(2016/09/28)
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- Effect of Substitution on the Aniline Moiety of the GPR88 Agonist 2-PCCA: Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies
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GPR88, an orphan receptor richly expressed in the striatum, is implicated in a number of basal ganglia-associated disorders. In order to elucidate the functions of GPR88, an in vivo probe appropriate for CNS investigation is required. We previously reported that 2-PCCA was able to modulate GPR88-mediated cAMP production through a Gαi-coupled pathway. Early structure-activity relationship (SAR) studies suggested that the aniline moiety of 2-PCCA is a suitable site for diverse modifications. Aimed at elucidating structural requirements in this region, we have designed and synthesized a series of analogues bearing a variety of substituents at the phenyl ring of the aniline moiety. Several compounds (e.g., 5j, 5o) showed improved or comparable potency, but have lower lipophilicity than 2-PCCA (clogP 6.19). These compounds provide the basis for further optimization to probe GPR88 in vivo functions. Computational studies confirmed the SAR trends and supported the notion that 4′-substituents on the biphenyl ring exit through a largely hydrophobic binding site to the extracellular loop.
- Jin, Chunyang,Decker, Ann M.,Harris, Danni L.,Blough, Bruce E.
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p. 1418 - 1432
(2016/10/31)
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- A rapid and efficient one-pot method for the reduction of N-protected α-amino acids to chiral α-amino aldehydes using CDI/DIBAL-H
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N-Protected amino acids can be easily converted into chiral α-amino aldehydes in a one-pot reaction by activation with CDI followed by reduction with DIBAL-H. This method delivers Boc-, Cbz- and Fmoc-protected amino aldehydes from proteinogenic amino acids in very good isolated yields and complete stereointegrity.
- Ivkovic, Jakov,Lembacher-Fadum, Christian,Breinbauer, Rolf
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supporting information
p. 10456 - 10460
(2015/11/10)
-
- Synthesis, pharmacological characterization, and structure - Activity relationship studies of small molecular agonists for the orphan GPR88 receptor
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GPR88 is an orphan G-protein-coupled receptor (GPCR) enriched in the striatum. Genetic deletion and gene expression studies have suggested that GPR88 plays an important role in the regulation of striatal functions and is implicated in psychiatric disorder
- Jin, Chunyang,Decker, Ann M.,Huang, Xi-Ping,Gilmour, Brian P.,Blough, Bruce E.,Roth, Bryan L.,Hu, Yang,Gill, Joseph B.,Zhang, X. Peter
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p. 576 - 587
(2014/08/05)
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- Samarium iodide-mediated Reformatsky reactions for the stereoselective preparation of β-hydroxy-γ-amino acids: Synthesis of isostatine and dolaisoleucine
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The synthesis of β-hydroxy-γ-amino acids via SmI 2-mediated Reformatsky reactions of α- chloroacetyloxazolidinones with aminoaldehydes is reported. Diastereoselective coupling is demonstrated to depend on the absolute configuration of the Evans chiral auxiliary employed in the reaction, allowing erythro or threo products to be obtained selectively. The potential utility of the methodology is exemplified by the facile synthesis of biologically relevant N-Boc-isostatine (2b) and N-Boc-dolaisoleucine (3c). This article not subject to U.S. Copyright. Published 2011 by the American Chemical Society.
- Nelson, Christopher G.,Burke, Terrence R.
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experimental part
p. 733 - 738
(2012/03/26)
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- Braces for the peptide backbone: Insights into structure-activity relationships of protease inhibitor mimics with locked amide conformations
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Flower power: Potent protease inhibitors containing triazolyl mimics of cis and trans backbone amides were engineered based on the structure of the sunflower trypsin inhibitor 1. The biologically relevant cis-Pro motif was successfully replaced with a non
- Tischler, Marco,Nasu, Daichi,Empting, Martin,Schmelz, Stefan,Heinz, Dirk W.,Rottmann, Philipp,Kolmar, Harald,Buntkowsky, Gerd,Tietze, Daniel,Avrutina, Olga
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supporting information; experimental part
p. 3708 - 3712
(2012/06/05)
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- Dipeptide Mimics, Libraries Combining Two Dipeptide Mimics with a Third Group, and Methods for Production Thereof
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Monovalent compounds having moieties comprising at least one amino acid side chain are bound to a core molecule, which also comprises a nucleophilic moiety bound to said core molecule. Monovalent compounds also comprise a macrocyclic ring, a nucleophilic
- -
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Page/Page column 49-50
(2012/09/22)
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- Universal peptidomimetics
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This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.
- Ko, Eunhwa,Liu, Jing,Perez, Lisa M.,Lu, Genliang,Schaefer, Amber,Burgess, Kevin
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supporting information; experimental part
p. 462 - 477
(2011/04/16)
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- Pyrrole-based scaffolds for turn mimics
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Two amino acid derived synthons were combined to give homopropargylic amines 2. Platinum dichloride was used to cyclize these intermediates into pyrroles 3 which collapsed to the target secondary structure mimics 1 on treatment with base. Side chains of these compounds overlay with an idealized type 1 β-turn and with an inverse γ-turn.(Figure Presented)
- Ko, Eunhwa,Burgess, Kevin
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supporting information; experimental part
p. 980 - 983
(2011/04/22)
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- Development of tetrahydroisoquinoline-based hydroxamic acid derivatives: Potent histone deacetylase inhibitors with marked in vitro and in vivo antitumor activities
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Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibitors (HDACi), among which compound 7d exhibited promising HDAC8 inhibitory and antiproliferative activities. Herein, we report the design and development of a new class of tetrahydroisoquinoline-bearing hydroxamic acid analogues as potential HDACi and anticancer agents. In vitro biological evaluation of these compounds showed improved HDAC8 inhibition (compounds 31a and 31b exhibited mid-nM IC50 values against HDAC8) and potent growth inhibition in multiple tumor cell lines. Most importantly, compounds 25e, 34a, and 34b exhibited excellent in vivo anticancer activities in a human breast carcinoma (MDA-MB-231) xenograft model compared with suberoylanilide hydroxamic acid (SAHA), an approved HDACi. Collectively, our results indicate that tetrahydroisoquinoline bearing a hydroxamic acid is an excellent template to develop novel HDACi as potential anticancer agents.
- Zhang, Yingjie,Feng, Jinhong,Jia, Yuping,Wang, Xuejian,Zhang, Lei,Liu, Chunxi,Fang, Hao,Xu, Wenfang
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scheme or table
p. 2823 - 2838
(2011/06/22)
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- MODULATORS OF G PROTEIN-COUPLED RECEPTOR 88
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The present disclosure is generally directed to compounds which can modulate G-protein coupled receptor 88, compositions comprising such compounds, and methods for modulating G-protein coupled receptor 88.
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Page/Page column 59-60
(2011/04/26)
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- Tin(ii) chloride assisted synthesis of N-protected γ-amino β-keto esters through semipinacol rearrangement
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A facile synthetic route for the preparation of N-protected γ-amino β-keto esters from amino aldehydes and ethyl diazoacetate is described. The two component coupling is facilitated by tin(ii) chloride followed by semipinacol rearrangement leading to the product in quantitative yield. The reaction is mild, instantaneous and compatible with Boc-, Fmoc- and Cbz-amino protecting groups.
- Bandyopadhyay, Anupam,Agrawal, Neha,Mali, Sachitanand M.,Jadhav, Sandip V.,Gopi, Hosahudya N.
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supporting information; experimental part
p. 4855 - 4860
(2010/12/24)
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- Antimicrobial metabolites produced by an intertidal Acremonium furcatum
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In a screening for antimicrobial metabolites, amides of d-allo- and l-isoleucine derivatives were isolated from the culture of a marine strain of Acremonium furcatum. Structural elucidation of these compounds was performed by analysis of spectroscopic data and confirmed by synthesis. All of the compounds, natural and synthetic intermediates, were bioassayed against bacteria and phytopathogenic fungi, with many showing remarkable antifungal activities.
- Gallardo, Gabriela L.,Butler, Matias,Gallo, Mariana L.,Rodriguez, M. Alejandra,Eberlin, Marcos N.,Cabrera, Gabriela M.
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p. 2403 - 2410
(2007/10/03)
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- Exploration of the P1 SAR of aldehyde cathepsin K inhibitors.
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The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S(1) subsite with a series of alpha-amino aldehyde derivatives substituted at the P(1) position afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.
- Catalano, John G,Deaton, David N,Furfine, Eric S,Hassell, Annie M,McFadyen, Robert B,Miller, Aaron B,Miller, Larry R,Shewchuk, Lisa M,Willard Jr., Derril H,Wright, Lois L
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p. 275 - 278
(2007/10/03)
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- Dipeptidyl peptidase IV inhibitors and their uses for lowering blood pressure levels
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The present invention provides new uses of DPIV-inhibitors of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, for lowering blood pressure levels.
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- Use of dipeptidyl peptidase IV inhibitors
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The present invention provides a new use of DP IV-inhibitors. The compounds of the present invention, and their corresponding pharmaceutically acceptable acid addition salt forms, are useful in treating conditions mediated by DP IV or DP IV-like enzymes, such as immune, autoimmune or central nervous system disorder selected from the group consisting of strokes, tumors, ischemia, Parkinson's disease and migraines. In a more preferred embodiment, the compounds of the present invention are useful for the treatment of multiple sclerosis.
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- Stereoselective synthesis, solution structure and metal complexes of (1S,2S)-2-amino-1-hydroxyalkylphosphonic acids
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The highly stereoselective synthesis of (1S,2S)-2-amino-1-hydroxyalkylphosphonic acids was achieved by addition of dimethyl phosphite to N-protected aminoaldehydes. Relative configuration and solution conformations of (1S,2S)-2-amino-1-hydroxy-alkylphosphonic acids (in D2O) and their dimethyl esters (in CDCl3 and CD3OD) were established by means of NMR basing on the dependence between observed values of coupling constants (3JHH, 3JPC, 3JHP) and corresponding dihedral angles. Potentiometric and spectroscopic methods were used for the evaluation of the structure of the complexes of (1S,2S)-2-amino-1-hydroxy-alkylphosphonic acids with Zn(II) and Cu(II) ions in aqueous solutions.
- Drag, Marcin,Latajka, Rafal,Gumienna-Kontecka, Elzbieta,Kozlowski, Henryk,Kafarski, Pawel
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p. 1837 - 1845
(2007/10/03)
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- Total syntheses of lyngbyabellins A and B, potent cytotoxic lipopeptides from the marine cyanobacterium Lyngbya majuscula
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The first total syntheses of lyngbyabellins A and B, Lyngbya majuscula derived lipopeptides, are described. The functionalized thiazole carboxylic acid units were prepared by the oxidative dehydrogenation of the corresponding thiazolidines with chemical manganese dioxide. The asymmetric synthesis of the dichlorinated β-hydroxy acid by a chiral oxazaborolidinone mediated aldol reaction. Finally, fragment condensation followed by macrolactamization provided lyngbyabellin A. The total synthesis of lyngbyabellin B was accomplished by formation of the sensitive thiazoline ring after the macrolactamization.
- Yokokawa, Fumiaki,Sameshima, Hirofumi,Katagiri, Daichi,Aoyama, Toyohiko,Shioiri, Takayuki
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p. 9445 - 9458
(2007/10/03)
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- Synthesis of new chiral peptide nucleic acid (PNA) monomers
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We have synthesised a series of new chiral type I peptide nucleic acid monomers in total yields of 36-53%, derived from Val, Ile, Ser(Bzl), Pro, and Trp, employing convenient procedure.
- Falkiewicz,Wisniowski,Kolodziejczyk,Wisniewski
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p. 1393 - 1397
(2007/10/03)
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- Discovery and parallel synthesis of a new class of cathepsin K inhibitors
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Peptidomimetic aminomethyl ketones have been identified as a new class of cathepsin K inhibitors. Traditional and high-speed parallel synthesis techniques were applied to investigate this series. Structure-activity relationships were established, and certain analogues were characterized with IC50 values in the range 200-500 nM.
- Smith, Roger A.,Bhargava, Ajay,Browe, Christopher,Chen, Jinshan,Dumas, Jacques,Hatoum-Mokdad, Holia,Romero, Romulo
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p. 2951 - 2954
(2007/10/03)
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- Difluoro ketone peptidomimetics suggest a large S1 pocket for Alzheimer's γ-secretase: Implications for inhibitor design
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The final step in the generation of the amyloid-β protein (Aβ), implicated in the etiology of Alzheimer's disease, is proteolysis within the transmembrane region of the amyloid precursor protein (APP) by γ-secretase. Although considered an important target for therapeutic design, γ-secretase has been neither well-characterized nor definitively identified. Previous studies in our laboratory using substrate-based difluoro ketone and difluoro alcohol transition-state analogue inhibitors suggest that γ-secretase is an aspartyl protease with loose sequence specificity. To further characterize the active site of γ-secretase, we prepared a series of difluoro ketone peptide analogues with varying steric bulkiness in the P1 position and tested the ability of these compounds to inhibit Aβ production in APP-transfected cells. Incorporation of bulky, aliphatic P1 side chains, such as sec-butyl or cyclohexylmethyl, led to increased α-secretase inhibitory potency, suggesting a large S1 pocket to accommodate these substituents and providing further evidence for loose sequence specificity. The cyclohexylmethyl P1 substituent allowed N-terminal truncation to a low-molecular-weight compound (50 ~ 5 μM). This finding suggests that optimal S1 binding may allow the development of potent inhibitors with ideal pharmaceutical properties. Moreover, a difluoro alcohol analogue with a cyclohexylmethyl P1 substituent was equipotent with its difluoro ketone counterpart, providing strong evidence that γ-secretase is an aspartyl protease. All new analogues inhibited total Aβ and Aβ42 production with the same rank order of potency and increased Aβ42 production at low concentrations, providing further evidence for distinct γ-secretases that are nevertheless closely similar with respect to active site topology and mechanism.
- Moore,Leatherwood,Diehl,Selkoe,Wolfe
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p. 3434 - 3442
(2007/10/03)
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- A second-generation cycloaddition route to 5-substituted 3-acyltetramic acids
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The 1,3-dipolar cycloaddition of α-aminonitrile oxides, formed from α- amino-acids, to enamines of β-ketoesters affords 3-(1-aminoalkyl)isoxazole- 4-carboxylic esters that are convened via pyrrolo[3,4-c]isoxazol-4-ones into 5-substituted 3-acetyltetramic
- Jones, Raymond C. F.,Dawson, Claire E.,O'Mahony, Mary J.
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p. 873 - 876
(2007/10/03)
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- PEPTIDE DERIVATIVES AND ANGIOTENSIN IV RECEPTOR AGONIST
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Short-chain peptide derivatives acting on angiotensin IV receptor at low concentrations. Because of agonistically acting on angiotensin IV receptor, the novel peptide derivatives of the present invention represented by the following formula (1) are useful as remedies for various diseases in which angiotensin IV participates:
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- Improvements relating to prodrugs
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A prodrug of the general formula FTLi-(PRT)m, where m is an integer from 1 to 5; FTLi is a ras inhibitor such as a farnesyltransferase inhibitor compound, such as Ia, Ib, Ic; and PRT represents m protecting groups or a precursor thereof, such as compound
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- Design of a potent combined pseudopeptide endothelin-a/endothelin-b receptor antagonist, ac-dBhg16-Leu-Asp-IIe-[NMe]IIe-Trp21 (PD 156252): Examination of its pharmacokinetic and spectral properties
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The endothelins (ETs) are a family of bicyclic 21-amino acid peptides that are potent and prolonged vasoconstrictors. It has been shown that highly potent combined ET(A)/ET(B) receptor antagonists can be developed from the C- terminal hexapeptide of ET (H
- Cody, Wayne L.,He, John X.,Reily, Michael D.,Haleen, Stephen J.,Walker, Donnelle M.,Reyner, Eric L.,Stewart, Barbra H.,Doherty, Annette M.
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p. 2228 - 2240
(2007/10/03)
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- Inhibitors of farnesyl-protein transferase
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The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invent
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- Synthesis of Chiral N-Protected α-Amino Aldehydes by Reduction of N-Protected N-Carboxyanhydrides (UNCAs)
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A facile one step synthesis of a wide variety of N-protected (Boc, Z, Fmoc) α-amino aldehydes under mild conditions is described.Pure N-protected (Boc, Z, Fmoc) α-amino aldehydes were obtained in high yields by reduction of N-protected (Z, Boc, Fmoc)-N-ca
- Fehrentz, Jean-Alain,Pothion, Catherine,Califano, Jean-Christophe,Loffet, Albert,Martinez, Jean
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p. 9031 - 9034
(2007/10/02)
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- Synthetic Laminin-like Peptides and Pseudopeptides as Potential Antimetastatic Agents
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This paper desribes our efforts to study structure-activity relationships, improve the antimetastatic potency, and limit the in vivo enzymatic degradation of YIGSR-NH2, a synthetic peptide from the B1 chain of laminin, which reportedly has potential as an
- Zhao, Ming,Kleinman, Hynda K.,Mokotoff, Michael
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p. 3383 - 3388
(2007/10/02)
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- INHIBITORS OF FARNESYL PROTEIN TRANSFERASE
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The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.
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- New Methods and Reagents in Organic Synthesis. 67. A General Synthesis of Derivatives of Optically Pure 2-(1-Aminoalkyl)thiazole-4-carboxylic Acids
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Preparations of 2-(1-aminoalkyl)thiazole-4-carboxylic acids (thiazole amino acids), important constituents of a series of cytotoxic cyclic peptides from marine organisms, have been conveniently and efficiently achieved as their N- and C-protected derivatives 6 from N-Boc or N-Z α-amino acids 1 in five steps.Esterification of 1 with methyl iodide followed by reduction with lithium chloride-sodium borohydride afforded N-protected amino alcohols 3.Selective reduction of the α-ester functions of the glutamic acid derivatives (Z-D- and Z-L-Glu(O-t-Bu)-OMe and O-t-Bu) was also achieved under the above reduction conditions.Dimethyl sulfoxide oxidation, followed by condensation with cysteine methyl ester afforded the thiazolidine derivatives 5, which were conveniently dehydrogenated with manganese dioxide, called chemical manganese dioxide (CMD) and produced for batteries, to give the desired thiazole amino acid derivetives 6.The glutamine derivatives (Z-D- and Z-L-(gln)Thz-OMe) were prepared from the corresponding glutamic acid derivatives (Z-D- and Z-L-6f).No appreciable racemization was observed in the above conversion, which was proven by HPLC of the 3,5-dinitrobenzoyl derivatives of thiazole amino acids 6 using a chiral column.
- Hamada, Yasumasa,Shibata, Makoto,Sugiura, Tsuneyuki,Kato, Shinji,Shioiri, Takayuki
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p. 1252 - 1255
(2007/10/02)
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