901773-68-0Relevant academic research and scientific papers
Phosphonic pseudopeptides as human neutrophil elastase inhibitors - A combinatorial approach
Sieńczyk, Marcin,Podgórski, Dawid,B?aejewska, Aleksandra,Kulbacka, Julita,Saczko, Jolanta,Oleksyszyn, Józef
experimental part, p. 1277 - 1284 (2011/04/12)
Here we present a simple and rapid method for the construction of phosphonic peptide mimetic inhibitor libraries - products of Ugi and Passerini multicomponent condensations - leading to the selection of new biologically active phosphonic pseudopeptides.
Synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters
Sieńczyk, Marcin,Kliszczak, Maciej,Oleksyszyn, Józef
, p. 4209 - 4211 (2007/10/03)
This letter describes the first example of the synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters. This method produces the title compounds in high purity and in very good yields. It also permits the generation of an α-aminopho
Remote binding energy in antibody catalysis: Studies of a catalytically unoptimized specificity pocket
Wade, Herschel,Scanlan, Thomas S.
, p. 1434 - 1443 (2007/10/03)
Binding interactions remote from the hydrolytic reaction center have been probed with substrate and phosphonate transition state analogues to understand how these types of interactions are used to promote catalysis in the 17E8 system. We find that the hapten-generated recogniton pocket in 17E8 has properties that are analogous to those of specificity pockets in enzymes. We have also found that there are specific requirements to form catalytically productive interactions between the side chain and the recognition pocket including conformation, size, and geometry. An additional requirement includes favorable simultaneous interactions between the side chain and binding pocket along with favorable interactions with the oxyanion hole. The 17E8 side chain recognition pocket seems to be less catalytically efficient than analogous pockets in enzymatic systems. The apparent binding energy gained from the methylene-pocket interactions in the 17E8 system is significantly smaller than those observed in natural enzymes. Furthermore, 17E8 does not use specific interactions in the recognition pocket to significantly affect catalytic turnover (kcat) which is thought to be a trait of an unoptimized catalyst. Analysis of the crystal structure of the 17E8·hapten complex has allowed for the identification of differences between the active sites of 17E8 and several proteases. The identified differences give insight to the sources of the inefficient use of binding energy.
