269399-46-4Relevant academic research and scientific papers
Peptidyl epoxides extended in the P′ direction as cysteine protease inhibitors: Effect on affinity and mechanism of inhibition
Perlman, Nurit,Hazan, Maya,Shokhen, Michael,Albeck, Amnon
experimental part, p. 9032 - 9039 (2009/04/04)
Endo peptidyl epoxides, in which the central epoxidic moiety replaces the scissile amide bond of a P3-P3′ peptide, were designed as cysteine proteases inhibitors. The additional P′-S′ interactions, relative to those of an exo peptidyl epoxide of the same P3-P1 sequence, significantly improved affinity to the enzymes papain and cathepsin B, but also changed the mode of inhibition from active-site directed inactivation to reversible competitive inhibition. Computational models rationalize the binding affinity and the inhibition mechanism.
Epoxidation of peptidyl olefin isosteres. Stereochemical induction effect of chiral centers at four adjacent C(α) positions
Perlman, Nurit,Livneh, Mordechai,Albeck, Amnon
, p. 1505 - 1516 (2007/10/03)
Four tripeptidyl olefin isosteres were prepared, each of which contains a single chiral center derived from the bulky amino acid phenylalanine at positions corresponding to the P2-P'2 positions of a protease substrate. The effect of these chiral centers on the stereochemical outcome of mCPBA epoxidation of the olefin functionality was studied. A chiral center at P2 or P'2 position has no significant effect, and the P'1 position exerts a small stereoselectivity. A chiral center at the P1 position, on the other hand, has a profound chiral induction effect on the epoxidation reaction. (C) 2000 Elsevier Science Ltd.
