- 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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- Synthesis, Characterization and in vitro Studies of a Cathepsin B-Cleavable Prodrug of the VEGFR Inhibitor Sunitinib
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Since several decades, the prodrug concept has raised considerable interest in cancer research due to its potential to overcome common problems associated with chemotherapy. However, for small-molecule tyrosine kinase inhibitors, which also cause severe side effects, hardly any strategies to generate prodrugs for therapeutic improvement have been reported so far. Here, we present the synthesis and biological investigation of a cathepsin B-cleavable prodrug of the VEGFR inhibitor sunitinib. Cell viability assays and Western blot analyses revealed, that, in contrast to the non-cathepsin B-cleavable reference compound, the prodrug shows activity comparable to the original drug sunitinib in the highly cathepsin B-expressing cell lines Caki-1 and RU-MH. Moreover, a cathepsin B cleavage assay confirmed the desired enzymatic activation of the prodrug. Together, the obtained data show that the concept of cathepsin B-cleavable prodrugs can be transferred to the class of targeted therapeutics, allowing the development of optimized tyrosine kinase inhibitors for the treatment of cancer.
- Karnthaler-Benbakka, Claudia,Koblmüller, Bettina,Mathuber, Marlene,Holste, Katharina,Berger, Walter,Heffeter, Petra,Kowol, Christian R.,Keppler, Bernhard K.
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- The Cooperative Effect of Both Molecular and Supramolecular Chirality on Cell Adhesion
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Although helical nanofibrous structures have great influence on cell adhesion, the role played by chiral molecules in these structures on cells behavior has usually been ignored. The chirality of helical nanofibers is inverted by the odd–even effect of methylene units from homochiral l-phenylalanine derivative during assembly. An increase in cell adhesion on left-handed nanofibers and weak influence of cell behaviors on right-handed nanofibers are observed, even though both were derived from l-phenylalanine derivatives. Weak and negative influences on cell behavior was also observed for left- and right-handed nanofibers derived from d-phenylalanine, respectively. The effect on cell adhesion of single chiral molecules and helical nanofibers may be mutually offset.
- Liu, Jinying,Yuan, Feng,Ma, Xiaoyu,Auphedeous, Dang-i Y.,Zhao, Changli,Liu, Chuntai,Shen, Changyu,Feng, Chuanliang
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supporting information
p. 6475 - 6479
(2018/05/08)
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- Binding and Action of Amino Acid Analogs of Chloramphenicol upon the Bacterial Ribosome
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Antibiotic chloramphenicol (CHL) binds with a moderate affinity at the peptidyl transferase center of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving properties of this inhibitor, we explored ribosome binding and inhibitory activity of a number of amino acid analogs of CHL. The L-histidyl analog binds to the ribosome with the affinity exceeding that of CHL by 10 fold. Several of the newly synthesized analogs were able to inhibit protein synthesis and exhibited the mode of action that was distinct from the action of CHL. However, the inhibitory properties of the semi-synthetic CHL analogs did not correlate with their affinity and in general, the amino acid analogs of CHL were less active inhibitors of translation in comparison with the original antibiotic. The X-ray crystal structures of the Thermus thermophilus 70S ribosome in complex with three semi-synthetic analogs showed that CHL derivatives bind at the peptidyl transferase center, where the aminoacyl moiety of the tested compounds established idiosyncratic interactions with rRNA. Although still fairly inefficient inhibitors of translation, the synthesized compounds represent promising chemical scaffolds that target the peptidyl transferase center of the ribosome and potentially are suitable for further exploration.
- Tereshchenkov, Andrey G.,Dobosz-Bartoszek, Malgorzata,Osterman, Ilya A.,Marks, James,Sergeeva, Vasilina A.,Kasatsky, Pavel,Komarova, Ekaterina S.,Stavrianidi, Andrey N.,Rodin, Igor A.,Konevega, Andrey L.,Sergiev, Petr V.,Sumbatyan, Natalia V.,Mankin, Alexander S.,Bogdanov, Alexey A.,Polikanov, Yury S.
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p. 842 - 852
(2018/02/26)
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- New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons
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An effective endocrine therapy for breast cancer is to selectively and effectively degrade the estrogen receptor (ER). Up until now, there have been largely only two molecular scaffolds capable of doing this. In this study, we have developed new classes of scaffolds that possess selective estrogen receptor degrader (SERD) and ER antagonistic properties. These novel SERDs potently inhibit MCF-7 breast cancer cell proliferation and the expression of ER target genes, and their efficacy is comparable to Fulvestrant. Unlike Fulvestrant, the modular protein-targeted chimera (PROTAC)-type design of these novel SERDs should allow easy diversification into a library of analogs to further fine-tune their pharmacokinetic properties including oral availability. This work also expands the pool of currently available PROTAC-type scaffolds that could be beneficial for targeted degradation of various other therapeutically important proteins.
- Wang, Lucia,Guillen, Valeria S.,Sharma, Naina,Flessa, Kevin,Min, Jian,Carlson, Kathryn E.,Toy, Weiyi,Braqi, Sara,Katzenellenbogen, Benita S.,Katzenellenbogen, John A.,Chandarlapaty, Sarat,Sharma, Abhishek
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supporting information
p. 803 - 808
(2018/07/21)
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- Photocyclization of Tetra- and Pentapeptides Containing Adamantylphthalimide and Phenylalanines: Reaction Efficiency and Diastereoselectivity
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A series of tetrapeptides and pentapeptides was synthesized bearing a phthalimide chromophore at the N-terminus. The C-terminus of the peptides was strategically substituted with an amino acid, Phe, Phe(OMe), or Phe(OMe)2 characterized by different oxidation potentials. The photochemical reactivity of the peptides was investigated by preparative irradiation and isolation of photoproducts, as well as with laser flash photolysis. Upon photoexcitation, the peptides undergo photoinduced electron transfer (PET) and decarboxylation, followed by diastereoselective cyclization with the retention of configuration for tetrapeptides or inversion of configuration for pentapeptides. Molecular dynamics (MD) simulations and NOE experiments enabled assignment of the stereochemistry of the cyclic peptides. MD simulations of the linear peptides disclosed conformational reasons for the observed diastereoselectivity, being due to the peptide backbone spatial orientation imposed by the Phe amino acids. The photochemical efficiency for the decarboxylation and cyclization is not dependent on the peptide length, but it depends on the oxidation potential of the amino acid at the C-terminus. The results described herein are particularly important for the rational design of efficient photochemical reactions for the preparation of cyclic peptides with the desired selectivity.
- Sohora, Margareta,Vazdar, Mario,Sovi?, Irena,Mlinari?-Majerski, Kata,Basari?, Nikola
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p. 14905 - 14922
(2019/01/04)
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- Synthesis and photochemical reactivity of phthalimidoadamantane–tyrosine conjugates
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Abstract: Dipeptide 3, tetrapeptide 4 and pentapeptide 5, containing adamantylphthalimide and tyrosine, were synthesized and their photochemical reactivity investigated. Upon excitation to the triplet excited state, 3 does not give any photoproduct, although the photoinduced electron transfer (PET) should take place based on the thermodynamic properties. Tetrapeptide 4 and pentapeptide 5 are photochemically reactive, undergoing decomposition upon excitation. The lack of anticipated photodecarboxylation reactivity is explained by PET between the tyrosine and the phthalimide. However, deprotonation of the phenoxyl radical-cation giving phenoxyl radicals or back electron transfer giving starting material are probably faster than intrastrand single electron transfer which would lead to carboxyl radical and decarboxylation. The results indicate the importance of fine-tuning the molecular structure to attain the desired photoreactivity by the right choice of the reactants redox potential, as well as their acid/base properties.
- Sohora, Margareta,Vidovi?, Nikolina,Mlinari?-Majerski, Kata,Basari?, Nikola
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p. 5305 - 5320
(2017/09/23)
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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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- N,O-Bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) as coupling agents for dipeptide synthesis
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A method using N,O-bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) as coupling agents for dipeptide synthesis is descried. The coupling reaction between N-hydroxysuccinimide (NHS) esters and amines could be performed under mild conditions with N,O-bis(trimethylsilyl)acetamide (BSA) as coupling reagent and no additional acid/base is required. All byproducts and excessive reactants are water soluble or hydrolysable and easy to eliminate through water-washing at the purification stage. Moreover, all the reactants are inexpensive and widely used in conventional drug production.
- Huang, Ye,Feng, Wen-Hua
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p. 357 - 360
(2016/03/16)
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- Encapsulation of a catalytic imidazolium salt into avidin: Towards the development of a biohybrid catalyst active in ionic liquids
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Herein, we report the development of biohybrid catalysts that are capable of catalyzing the aldol reaction. The use of biotinylated imidazolium salts in combination with racemic or enantiomerically pure catalytic anions allowed us to study the adaptive and cooperative positioning of the anionic catalyst inside the protein. Supramolecular encapsulation of the biotinylated catalyst into avidin resulted in good selectivity for the aldol reaction performed in ionic liquid/water mixtures. Biohybrid catalysts capable of catalyzing the aldol reaction are prepared from avidin and biotinylated imidazolium salts with either racemic or enantiomerically pure catalytic anions. Supramolecular encapsulation (see figure) of the biotinylated catalyst in avidin resulted in good selectivities for the aldol reaction when performed in ionic liquid/water mixtures and the adaptive and cooperative positioning of the anionic catalyst inside the avidin protein is discussed. Copyright
- Gauchot, Vincent,Branca, Mathieu,Schmitzer, Andreea
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p. 1530 - 1538
(2014/03/21)
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- Mechanistic insight into the lability of the benzyloxycarbonyl (Z) group in N-protected peptides under mild basic conditions
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An unexpected lability of the benzyloxycarbonyl (Z) protecting group under mild basic conditions at room temperature is explained by a mechanism based on anchimeric assistance. It is found that the vicinal amide group stabilises the tetrahedral intermediate formed after nucleophilic addition of hydroxide to the carbonyl of the Z group. This effect operates in N-protected tripeptides and tetrapeptides but Z-protected dipeptides are stable under the same conditions due to blockage of the vicinal amide NH by intramolecular H-bonding with the terminal carboxylate moiety. Copyright
- Tena-Solsona, Marta,Angulo-Pachon, Cesar A.,Escuder, Beatriu,Miravet, Juan F.
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supporting information
p. 3372 - 3378
(2014/06/09)
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- Evaluation of α,β-unsaturated ketone-based probes for papain-family cysteine proteases
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The field of activity-based proteomics makes use of small molecule active site probes to monitor distinct subsets of enzymatic proteins. While a number of reactive functional groups have been applied to activity-based probes (ABPs) that target diverse families of proteases, there remains a continual need for further evaluation of new probe scaffolds and reactive functional groups for use in ABPs. In this study we evaluate the utility of the, α,β-unsaturated ketone reactive group for use in ABPs targeting the papain-family of cysteine proteases. We find that this reactive group shows highly selective labeling of cysteine cathepsins in both intact cells and total cell extracts. We observed a variable degree of background labeling that depended on the type of tag and linker used in the probe synthesis. The relative ease of synthesis of this class of compounds provides the potential for further derivatization to generate new families of cysteine protease ABPs with unique specificity and labeling properties.
- Yang, Zhimou,Fonovic, Marko,Verhelst, Steven H.L.,Blum, Galia,Bogyo, Matthew
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scheme or table
p. 1071 - 1078
(2009/09/25)
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- Synthesis and biological evaluation of boron peptide analogues of Belactosin C as proteasome inhibitors
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A series of boron peptides 11, 13, 15 and 17 were designed and synthesized as proteasome inhibitors based on the structure of Belactosin C. Matteson homologation was a key step in the synthesis of the boron peptides. Compounds 11a and 13 showed significant inhibition of 20S proteasome chymotrypsin-like (β5) activity (IC50 = 0.28 and 0.51 μM, respectively). Furthermore, like PS-341, compound 11a increased the G2/M cell distribution. A biparametric cytofluorimetric analysis with FITC-labeled annexin V and propidium iodide showed induction of apoptosis by compound 11a at >1 μM concentrations of compound.
- Nakamura, Hiroyuki,Watanabe, Mizuyoshi,Ban, Hyun Seung,Nabeyama, Wataru,Asai, Akira
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scheme or table
p. 3220 - 3224
(2010/04/05)
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- Synthesis of potent water-soluble tissue transglutaminase inhibitors
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Dipeptide-based sulfonium peptidylmethylketones derived from 6-diazo-5-oxo-l-norleucine (DON) have been investigated as potential water-soluble inhibitors of extracellular transglutaminase. The lead compounds were prepared in four steps and exhibited pote
- Griffin, Martin,Mongeot, Alexandre,Collighan, Russell,Saint, Robert E.,Jones, Richard A.,Coutts, Ian G.C.,Rathbone, Daniel L.
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scheme or table
p. 5559 - 5562
(2009/05/30)
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- Synthesis and epimerization of phenylalanyl 4-aminocyclophosphamides
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Peptide and amino acid conjugates of (4R)- and (4S)-4-aminocyclophosphamides (4-NH2-CPA, 3) were designed as prodrug forms of phosphoramide mustard. Four diastereomers of Boc-Phe-4-NH-CPA (6) were synthesized stereospecifically from homoserine (R or S) and the protection strategy was optimized for the homoserine hydroxyl group during the construction of the 1,3,2-oxazaphosphorinane ring. The Phe-4-NH-CPA isomers of the trans-configuration ((2S,4R)- and (2R,4S)-) were found to be less stable than the corresponding isomers of the cis-configuration ((2R,4R)- and (2S,4S)-) and to undergo epimerization of the C-4 chiral center in the presence of 25% TFA used during Boc deprotection. The synthetic route developed should be applicable to the synthesis of a variety of peptide and amino acid conjugates of 4-aminocyclophosphamide.
- Jiang, Yongying,Zhang, Zhoupeng,DiPaola, Robert S.,Hu, Longqin
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p. 10637 - 10645
(2008/02/13)
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- 5′-O-[(N-acyl)sulfamoyl]adenosines as antitubercular agents that inhibit MbtA: An adenylation enzyme required for siderophore biosynthesis of the mycobactins
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A study of the structure - activity relationships of 5′-O-[N- (salicyl)sulfamoyl]adenosine (6), a potent inhibitor of the bifunctional enzyme salicyl-AMP ligase (MbtA, encoded by the gene Rv2384) in Mycobacterium tuberculosis, is described, targeting the salicyl moiety. A systematic series of analogues was prepared exploring the importance of substitution at the C-2 position revealing that a hydroxy group is required for optimal activity. Examination of a series of substituted salicyl derivatives indicated that substitution at C-4 was tolerated. Consequently, a series of analogues at this position provided 4-fluoro derivative, which displayed an impressive MIC 99 of 0.098 μM against whole-cell M. tuberculosis under iron-limiting conditions. Examination of other heterocyclic, cycloalkyl, alkyl, and aminoacyl replacements of the salicyl moiety demonstrated that these nonconserative modifications were poorly tolerated, a result consistent with the fairly strict substrate specificities of related non-ribosomal peptide synthetase adenylation enzymes.
- Qiao, Chunhua,Gupte, Amol,Boshoff, Helena I.,Wilson, Daniel J.,Bennett, Eric M.,Somu, Ravindranadh V.,Barry III, Clifton E.,Aldrich, Courtney C.
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p. 6080 - 6094
(2008/09/18)
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- Monomeric insulin
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This invention provides a novel monomeric insulin B27K-DTrI, B27K-destripeptide-Insulin) its composition and the method of preparation therefore. Highly pure B27K-DTrI-Insulin is monomeric (non-associative at high concentration and physiological pH) with in vivo bioactivity being 80% of that of native insulin. B27K-DTrI-Insulin can be produced by enzyme cleavage of a monomeric insulin precursor secreted by yeast instead of the less efficient enzyme transpeptidation as known in the prior art. The new method increases the total yield and is favorable for industrial production.
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- Procedure for the oxidation of β-amino alcohols to α-amino aldehydes
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A novel procedure for the mild oxidation of β-amino alcohols to α-amino aldehydes using commercially available manganese(IV) oxide is reported. There are several important advantages of the new method, such as high enantiopurity of the reaction and the absence of either over-oxidation or any reaction by-products during the process. A number of N-protected L-α-amino aldehydes was obtained. All new compounds were characterized by their NMR spectra and optical rotation data. Georg Thieme Verlag Stuttgart.
- Sergeev, Maxim E.,Pronin, Victor B.,Voyushina, Tatiana L.
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p. 2802 - 2804
(2007/10/03)
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- Synthesis and activity of 5′-uridinyl dipeptide analogues mimicking the amino terminal peptide chain of nucleoside antibiotic mureidomycin A
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A series of 5′-uridinyl dipeptides were synthesised which mimic the amino terminal chain of nucleoside antibiotic mureido omycin A. Aminoacyl-β-alanyl- and aminoacyl-N-methyl-β-alanyl- dipeptides were attached either via an ester linkage to the 5′-hydroxyl of uridine, or via an amide linkage to 5′-amino-5′-deoxyuridine. The most active inhibitor of Escherichia coli phospho-MurNAc-pentapeptide translocase (MraY) was 5′-O-(L-Ala-N-methyl-β-alanyl)-uridine (13l), which also showed 97% enzyme inhibition at 2.35 mM concentration, and showed antibacterial activity at 100 μg/mL concentration against Pseudomonas putida. Both the central N-methyl amide linkage and a 5′ uridine ester linkage were required for highest biological activity. Enzyme inhibition was shown to be competitive with Mg2+. It is proposed that the primary amino terminus of the inhibitor binds in place of the Mg2+ cofactor at the MraY active site, positioned via a cis-N-methyl amide linkage.
- Howard, Nigel I.,Bugg, Timothy D. H.
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p. 3083 - 3099
(2007/10/03)
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- New prolyl oligopeptidase inhibitors developed from dicarboxylic acid bis(L-prolyl-pyrrolidine) amides
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Isophthalic acid bis(L-prolyl-pyrrolidine) amide is a very potent prolyl oligopeptidase inhibitor, but it has a log P value of -0.2, which is very low for a compound targeted to the brain. Therefore, these types of compounds were further modified to improve the structure-activity relationships, with the focus on increasing the log P value. The inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. The most promising compounds resulted from replacing the pyrrolidinyl group at the P5 site by cycloalkyl groups, such as cyclopentyl and cyclohexyl groups, and by a phenyl group. These compounds are slightly more potent, and they have a significantly higher log P value. The potency of these compounds was further increased by replacing the pyrrolidinyl group at the P1 site by 2(S)-cyanopyrrolidinyl and 2(S)-(hydroxyacetyl)pyrrolidinyl groups.
- Wallén, Erik A. A.,Christiaans, Johannes A. M.,Jarho, Elina M.,Forsberg, Markus M.,Ven?l?inen, Jarkko I.,M?nnist?, Pekka T.,Gynther, Jukka
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p. 4543 - 4551
(2007/10/03)
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- Combinatorial synthesis through disulfide exchange: Discovery of potent psammaplin A type antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA)
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Psammaplin A is a symmetrical bromotyrosine-derived disulfide natural product isolated from the Psammaplysilla sponge, which exhibits in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Inspired by the structure of this marine natural product, a combinatorial scrambling strategy for the construction of heterodimeric disulfide analogues was developed and applied to the construction of a 3828-membered library starting from 88 homodimeric disulfides. These psammaplin A analogues were screened directly against various gram positive bacterial strains leading to the discovery of a series of potent antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA). Among the most active leads derived from these studies are compounds 104, 105, 113, 115, 123, and 128. The present, catalytically-induced, disulfide exchange strategy may be extendable to other types of building blocks bearing thiol groups facilitating the construction of diverse discovery-oriented combinatorial libraries.
- Nicolaou,Hughes, Robert,Pfefferkorn, Jeffrey A.,Barluenga, Sofia,Roecker
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p. 4280 - 4295
(2007/10/03)
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- Synthesis of N-alkoxycarbonyl-3-substituted tetramic acids and functionalized enols via C-acylation reactions of active methylene compounds with N-hydroxysuccinimide esters of N-alkoxycarbonyl-α-amino acids
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The N-hydroxysuccinimide esters of N-alkoxycarbonyl-α-amino acids react with active methylene compounds (malonic and acyl acetic esters), under basic conditions, to produce N-alkoxycarbonyl-3-substituted tetramic acids 7-17; in the case of the N-hydroxysuccinimide ester of L-alanine, the corresponding optically active tetramic acids 15 and 16 are obtained. In addition, the C-acylation reactions of cyanoacetic esters furnishes the functionalized enols 18-23 in very good yields. Spectral data and physical characteristics for all compounds are reported.
- Detsi, Anastasia,Micha-Screttas, Maria,Igglessi-Markopoulou, Olga
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p. 2443 - 2449
(2007/10/03)
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- Peptide inhibitors of IκB protease: Modification of the C-termini of Z-LLF-CHO
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A series of tripeptides (Z-LLF-R) with various modifications at their C-terminus were synthesized and evaluated for their ability to prevent the activation of NF-κB through inhibition of IκB protease. Of the compounds evaluated only the C-terminal aldehydes 5a,b were active in our Jurkat T-cell based assay. Compounds 5a also decreased IL-2 and IL-8 levels in these cells indicating that inhibitors of IκB protease can have an effect on various signalling pathways.
- Suto, Mark J.,Sullivan, Robert W.,Ransone, Lynn J.
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p. 2925 - 2930
(2007/10/03)
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- An improved method for the synthesis of active esters of N-protected amino acids and subsequent synthesis of dipeptides
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4-Dimethylaminopyridine-catalyzed reaction of mixed carbonates 3 with N-protected amino acids 4 gave the corresponding active esters 5-9, from which dipeptides 11-18 were synthesized by aminolysis with amino acids 10.
- Takeda,Ayabe,Suzuki,Konda,Harigaya
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p. 689 - 691
(2007/10/02)
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- ASYMMETRIC SYNTHESIS OF AMINO ACIDS VIA THE CATALYTIC REDUCTION OF ACYLAMINOACRYLIC ACID AZLACTONE DERIVATIVES. 24. REDUCTIVE AMINOLYSIS OF 2-METHYL-4-BENZYLIDENE-Δ2-OXAZOLIN-5-ONE UPON TREATMENT WITH A CATALYTIC SYSTEM BASED ON S-PHENYLALANINE DERIVATIVES
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Reductive aminolysis of 2-methyl-4-benzylidene-Δ2-oxazolin-5-one upon treatment with a PdCl2-S-phenylalanine ester (dimethylamide) catalytic system leads to the formation of the corresponding acylated dipeptide derivatives, with the R,S-configuration (diastereomer) predominating (DE 9-27percent).The reaction stereoselectivity in dimethoxyethane increases sharply in the presence of triethylamine additive, and in the case of S-phenylalanine methyl ester reaches 47percent.The stepwise mechanism for this process has been studied.
- Lyubeznova, M. R.,Karpeiskaya, E. I.,Klabunovskii, E. I.
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p. 720 - 726
(2007/10/02)
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- Novel Preparation of N-Protected Amino Acid Active Esters Using 1,2,2,2-Tetrachloroethyl Carbonates
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1,2,2,2-Tetrachloroethyl chloroformate reacts with substituted phenols or N-hydroxy imides to yield crystalline and stable mixed aryl or oximido tetrachloroethyl carbonates.When allowed to react with an N-protected amino acid derivative, these compounds proved to be efficient for the syntheses of the corresponding active esters.A series of active esters including p-nitrophenol, trichlorophenol, pentafluorophenol, and N-hydroxysuccinimide derivatives were prepared by this new procedure.
- Jaoudai, Mahmoud,Martinez, Jean,Castro, Bertrand
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p. 2364 - 2367
(2007/10/02)
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- LE CHLOROFORMIATE D'ISOPROPENYLE (IPCF) EN CHIMIE DES AMINO-ACIDES ET DES PEPTIDES - III SYNTHESE D'ESTERS ACTIFS D'AMINO ACIDES N-PROTEGES
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Isopropenyl chloroformate (IPCF) was used for preparation of mixed carbonates (Aryl and isopropenyl) which are very suitable reagents for active ester synthesis of amino acid derivatives (Boc derivatives in particular).
- Jaouadi, M.,Selve, C.,Dormoy, J. R.,Castro, B.,Martinez, J.
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p. 1721 - 1722
(2007/10/02)
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- SYNTHESIS OF AMINO ACID BONDED SILICA GEL VIA ACTIVE ESTER WITH N-HYDROXYSUCCINIMIDE
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The surface of silica gel was chemically modified by amino acid via active ester with N-hydroxysuccinimide.The formations of insoluble by-product and fine particle coming from silica gel, which occur in DCC method were avoided.The amounts of amino acid coupling to silica gel were about twice larger than that by DCC method.
- Watanabe, Noriyuki
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p. 1331 - 1332
(2007/10/02)
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