34002-94-3Relevant academic research and scientific papers
Towards the identification of unknown neuropeptide precursor-processing enzymes: Design and synthesis of a new family of dipeptidyl phosphonate activity probes for substrate-based protease identification
Sabidó, Eduard,Tarragó, Teresa,Giralt, Ernest
supporting information; experimental part, p. 8350 - 8355 (2011/02/22)
Specific proteolytic processing of inactive precursors is an exquisite cellular mechanism that triggers the activation of numerous physiologic peptides and proteins. This process ensures the generation of biologically active peptides, such as many neurope
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.
Synthesis and proteinase inhibitory properties of diphenyl phosphonate analogues of aspartic and glutamic acids
Hamilton, Robert,Walker, Brian,Walker, Brian J.
, p. 1655 - 1660 (2007/10/03)
The synthesis of diphenyl phosphonate analogues of aspartic and glutamic acid, and their inhibitory activity against S. aureus V8 protease and granzyme B, is described. The study has revealed difficulties with protecting group compatibility in the synthesis of these analogues. Two analogues, Acetyl.Asp(P)(OPh)2 and Acetyl.Glu(P)(OPh)2 were found to function as irreversible inactivators of V8 proteinase, yet exhibit no activity against granzyme B.
Phosphonic acid and phosphinic acid tripeptides as inhibitors of glutathionylspermidine synthetase
Verbruggen, Christophe,De Craecker, Sofie,Rajan, Padinchare,Jiao, Xian-Yun,Borloo, Marianne,Smith, Keith,Fairlamb, Alan H.,Haemers, Achiel
, p. 253 - 258 (2007/10/03)
A series of phosphonic and phosphinic acid derivatives of glutathione were synthesized as potential inhibitors of glutathionylspermidine synthetase, an essential enzyme in the biosynthesis of trypanothione in trypanosomatids. The compounds showed moderate activity. Copyright
Synthesis of diphenyl phosphonate analogues of tyrosine and tryptophan and derived peptides as chymotrypsin inhibitors
Bergin, Carol,Hamilton, Robert,Walker, Brian,Walker, Brian J.
, p. 1155 - 1156 (2007/10/03)
The synthesis of α-aminophosphonate analogues of tyrosine and tryptophan, e.g. 4 and 5 respectively, and their incorporation into proline-containing dipeptides is reported; of the sequences synthesised, the dipeptide Z-Pro-Trp(P)(OPh)2 is the o
Cephalosporin compounds
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, (2008/06/13)
Novel 7-azido-3-cephem compounds are prepared via α-amino-phosphonoacetate esters. The cephem compounds are intermediates for the preparation of novel and known useful antibiotic cephalosporins.
