92235-34-2Relevant articles and documents
Protein synthesis with conformationally constrained cyclic dipeptides
Bai, Xiaoguang,Dedkova, Larisa M.,Hecht, Sidney M.,Zhang, Chao
supporting information, (2020/10/02)
We have synthesized several conformationally constrained dipeptide analogues as possible substrates for incorporation into proteins. These have included three cyclic dipeptides formed from Boc derivatives of 2,4-diaminobutyric acid, ornithine and lysine, having 5-, 6-, and 7-membered lactam rings, respectively. These dipeptides were used to activate a suppressor tRNA transcript, the latter of which had been prepared by in vitro transcription. Using modified E. coli ribosomes described previously, these activated suppressor tRNAs enabled the incorporation of the three cyclic dipeptides into dihydrofolate reductase (DHFR) at positions 18 and 49. The suppression yields increased with increasing lactam ring size and were found to proceed in suppression yields ranging from 3.4 to 8.9% at two different protein sites for the 5-, 6- and 7-membered lactam dipeptides. The greater facility of incorporation of the 7-membered lactam prompted us to prepare two 7-membered cyclic acylhydrazides (4 and 5) by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI)-mediated cyclization of amino acids having selectively protected hydrazine functional groups in their side chains. In common with the lactam dipeptides, acylhydrazide dipeptides 4 and 5 could be used to activate the same suppressor tRNA transcript and to incorporate the cyclic dipeptides into DHFR. They were incorporated into the same two DHFR sites in suppression yields ranging from 8.3 to 11.2%.
Concise and efficient synthesis of highly potent and selective dipeptidyl peptidase II inhibitors
Rasheed, Abdul M.,Namala, Rambabu,Manne, Narendra,Vanjivaka, Sreelatha,Dhamjewar, Ravi,Balasubramanian, Gopalan
, p. 162 - 169 (2008/03/17)
Highly potent and selective DPP II inhibitors N'-(4-Chlorobenzyl)-N'- methyl-4-oxo-4-(1-piperidinyl)-1,3-(S)-butane-diamine dihydrochloride 1 and N'-(4-chlorobenzyl)-4-oxo-4-(1-piperidinyl)-1,3-(S)-butanediamine dihydrochloride 2 have been efficiently synthesized starting from L-glutamine. A short and high yielding route with simple isolation techniques has been disclosed. Copyright Taylor & Francis Group, LLC.
Design and structure-activity relationships of potent and selective inhibitors of blood coagulation factor Xa
Ewing, William R.,Becker, Michael R.,Manetta, Vincent E.,Davis, Roderick S.,Pauls, Henry W.,Mason, Helen,Choi-Sledeski, Yong Mi,Green, Daniel,Cha, Don,Spada, Alfred P.,Cheney, Daniel L.,Mason, Jonathan S.,Maignan, Sebastien,Guilloteau, Jean-Pierre,Brown, Karen,Colussi, Dennis,Bentley, Ross,Bostwick, Jeff,Kasiewski, Charles J.,Morgan, Suzanne R.,Leadley, Robert J.,Dunwiddie, Christopher T.,Perrone, Mark H.,Chu, Valeria
, p. 3557 - 3571 (2007/10/03)
The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(s)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (K1 = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.
