2592-22-5Relevant articles and documents
Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 2. Peptide structure- activity studies
Dragovich, Peter S.,Webber, Stephen E.,Babine, Robert E.,Fuhrman, Sheila A.,Patick, Amy K.,Matthews, David A.,Reich, Siegfried H.,Marakovits, Joseph T.,Prins, Thomas J.,Zhou, Ru,Tikhe, Jayashree,Littlefield, Ethel S.,Bleckman, Ted M.,Wallace, Michael B.,Little, Thomas L.,Ford, Clifford E.,Meador III, James W.,Ferre, Rose Ann,Brown, Edward L.,Binford, Susan L.,DeLisle, Dorothy M.,Worland, Stephen T.
, p. 2819 - 2834 (2007/10/03)
The structure-based design, chemical synthesis, and biological evaluation of various peptidederived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s-1 and antiviral EC50's which approach 0.15 μM. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s-1) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 μM). A 1.9 A? crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-2 3CP is also detailed.
Cyclo-((S)-leucyl-(S)-histidyl). A Catalyst for Asymmetric Addition of Hydrogen Cyanide to Aldehydes
Mori, Atsunori,Ikeda, Yoshitaka,Kinoshita, Koichi,Inoue, Shohei
, p. 2119 - 2122 (2007/10/02)
Asymmetric addition of hydrogen cyanide to various aldehydes in the presence of a catalytic amount of cyclo-((S)-leucyl-(S)-histidyl) affords the corresponding cyanohydrins in moderate to good optical yields.The reaction of benzaldehyde with hydrogen cyanide gives (S)-2-hydroxy-2-phenylacetonitrile (85percent, 55percent ee) whose stereochemistry is found to be opposite to our previous result using cyclo-((S)-phenylalanyl-(S)-histidyl).
