- Synthesis of new l-proline amides with anticonvulsive effect
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Series of heterocyclic L-proline amides were prepared from BOC-L-proline and heterocyclic amines (mostly substituted piperazines and morpholines) via active ester with hydroxysuccinimide. 4-(4-Fluorobenzoyl)piperidine afforded L-proline 4-(4-(4-(4-fluorobenzoyl)piperidin-1-yl)benzoyl)piperidine (7b) simultaneously with expected L-proline 4-(4-fluorobenzoyl)piperidide (7a). D-Proline N-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)amide (2) was prepared starting from D-proline. The amides were tested by methods of biochemical and behavioural pharmacology.
- Silhankova, Alexandra,Sindelar, Karel,Dobrovsky, Karel,Krejci, Ivan,Hodkova, Jarmila,Polivka, Zdenek
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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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- 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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- Catalytic anions embedded into avidin: Importance of their chirality and the chiral environment on the stereocontrol of the aldol reaction
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Several catalytic anions bearing a pseudo-dipeptide scaffold, in combination with a biotinylated imidazolium cation, were prepared. The assembly of these salts with avidin resulted in the formation of stable biohybrid catalysts, active in ionic liquid/aqueous media for the aldol reaction. By using natural and non-natural amino alcohols as "side chains" for the proline derivative anion, we studied the cooperativity between the anion and its position in avidin. Taking advantage of the large freedom of movement of the anion inside avidin, we also investigated the substrate scope of this type of biohybrid catalyst.
- Gauchot, Vincent,Schmitzer, Andreea R.
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p. 2694 - 2701
(2014/04/17)
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- A facile synthesis and crystallographic analysis of N-protected β-amino alcohols and short peptaibols
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A facile, efficient and racemization-free method for the synthesis of N-protected β-amino alcohols and peptaibols using N-hydroxysuccinimide active esters is described. Using this method, dipeptide, tripeptide and pentapeptide alcohols were isolated in high yields. The conformations in crystals of β-amino alcohol, dipeptide and tripeptide alcohols were analysed, with a well-defined type III β-turn being observed in the tripeptide alcohol crystals. This method is found to be compatible with Fmoc-, Boc- and other side-chain protecting groups.
- Jadhav, Sandip V.,Bandyopadhyay, Anupam,Benke, Sushil N.,Mali, Sachitanand M.,Gopi, Hosahudya N.
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supporting information; experimental part
p. 4182 - 4187
(2011/06/28)
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- VLA-4 inhibitor: oMePUPA-V
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OMePUPA-V, (R)-N-[[4-[[(2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L-prolyl-3-methyl)-β-Alanine, a cell adhesion inhibitor, pharmaceutical compositions, and methods of treatment of cell-adhesion mediated pathologies.
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- β-lactam derivatives as enzyme inhibitors: Carboxy peptidyl derivatives of (S)-4-Oxoazetidine-2-carboxylate as peptidomimetics
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4-Oxoazetidine-2-carboxylic acid, protected at the nitrogen by silyl groups, was coupled with amino acid and oligopeptide esters. Desilylation and deprotection of the amino acid residues yielded the free β-lactam peptides. Structure and properties were elucidated by spectroscopic methods and discussed. Some selected compounds Were tested as fibrinogen inhibitors and for thrombocyte aggregation. None of the compounds showed any activity up to a concentration of 10-5 Mol/1. Some other compounds exhibited a weak inhibitory activity against elastase (PPE).
- Schneider, Martin,Otto, Hans-Hartwig
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p. 167 - 172
(2007/10/03)
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- Synthesis of N-hydroxysuccinimide esters using polymer bound HOBT
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The preparation of the N-hydroxysuccinimide esters via reactions mediated by polymer bound 1-hydrozybenzotriazole (HOBT) is reported.
- Dendrinos, Kleanthis G.,Kalivretenos, Aristotle G.
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p. 1321 - 1324
(2007/10/03)
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- Stabilized analogs of thymopentin. 1. 4,5-Ketomethylene pseudopeptides
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The pentapeptide, thymopentin (Arg1-Lys2-Asp3-Val4-Tyr5) is known for its activity as an immunomodulating drug, but with limited half-life in plasma. In this first paper of a series of three studies, the synthesis of analogs stabilized at the peptide bond between the C-terminal amino acids via insertion of a ketomethylene moiety is described. N-Blocked pseudopeptides containing Val(k)Phe, Ala(k)Phe, and Val(k)Val units were prepared and attached to chloromethyl Merrifield resin via the carboxy terminal. Removal of the N-BOC group by trifluoroacetic acid was followed by sequential coupling with N-BOC dipeptides of aspartic acid to yield resin-bound N-BOC pseudotetrapeptides. Removal of N-BOC and coupling with N-BOC-r-N- tosylarginine followed by total cleavage of blocking groups and resin by HF afforded the target pseudopentapeptides. The analogs were found to compete favorably with thymopentin for binding to CEM cells, but binding was reduced by about 20-30% on average. All analogs showed significant enhancement of half-life versus thymopentin in mouse serum, but most showed only modest improvement in human serum. Insertion of proline or norleucine at position 2 in the chain caused a substantial increase in half-life (3-4-fold), while N- methylnorleucine conferred complete stability in the analogs.
- DeGraw, Joseph I.,Almquist, Ronald G.,Hiebert, Charles K.,Colwell, William T.,Crase, Jac,Hayano, Takeshi,Judd, Amrit K.,Dousman, Linda,Smith, R. Lane,Waud, William R.,Uchida, Itsuo
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p. 2386 - 2397
(2007/10/03)
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- Heterocyclic amines useful in the therapy of asthma and imflammation of the respiratory tract
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Compounds of the formula STR1 wherein A, Y, X, B and D are described in the specification are disclosed. The compounds possess activity in treating asthma and other pathologies of the respiratory tract.
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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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