2592-22-5Relevant academic research and scientific papers
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.
Thermodynamic and (1)H NMR Study of Proton Complex Formation of Histidine-containing Cyclodipeptides in Aqueous Solution
Arena, Giuseppe,Impellizzeri, Giuseppe,Maccarrone, Giuseppe,Pappalardo, Giuseppe,Sciotto, Domenico,Rizzarelli, Enrico
, p. 371 - 376 (2007/10/02)
A thermodynamic and (1)H NMR study of proton complex formation in aqueous solution of some L-histidine-containing cyclic L-dipeptides has been carried out.The enthalpic and entropic changes associated with protonation of the cyclodipeptides, obtained by potentiometric and calorimetric measurements, together with the (1)H NMR data and NOESY experiments, enable the role played by non-covalent interactions in proton complex formation to be assessed.In addition, a comparison with c(Gly-His) permits the influence of side-chain residues on the conformation of protonated species to be observed.
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).
