摘要:

The bis‐cysteinyl hinge‐fragment 225–232 of human IgG1 has been extended at theN‐ orC‐terminus with Nle15‐desamido‐human‐little‐gastrin‐[5‐17] and Nle15‐human‐little‐gastrin‐[5‐17]‐NH2, respectively. Thermodynamically controlled air oxidation of the resulting bis‐cysteinyl‐peptides led to the predominant formation of the corresponding dimers in parallel alignment despite the incorporation of the immunoglobulin‐unrelated gastrin‐sequences. These surprising results confirm the high degree of structural information inherent in the hinge‐sequence and its intrinsic tendency to fold into the correct structure in terms of cysteine pairings. This protein subdomain‐the hinge‐peptide‐is therefore well suited as core molecule for the design of fully synthetic immunogens w

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00734.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The nonapeptide, HSV R2‐(329‐337). corresponding to the subunit 2 (R2) carboxyl terminus of herpes simplex virus (HSV) ribonucleotide reductases, specifically inhibits this enzyme activity. We report here that under standard reductase assay conditions, this peptide was rapidly degraded by proteases present in the partially purified enzyme extract. The main process of proteolysis involves the successive removal of Tyr329and Ala330, which corresponds to an aminopeptidase activity. Determination of the proteolytic susceptibility of HSV R2‐(329‐337) analogs showed that natural modifications which are present in the homologous varicella zoster virus (VZV) nonapeptide decreased its susceptibility to protease action 1.5‐fold.Nα‐acetylation, a modification known to protect peptides against aminopeptidase attacks, greatly improved the proteolytic resistance of HSV and VZV nonapeptides. Moreover, Ac‐VZV R2‐(298‐306) exhibited a 15‐fold higher potency on reductase inhibition than HSV R2‐(329‐337). The degradation process of HSV R2‐(329‐337) was partially inhibited by amastatin. bestatin, and leupeptin whereas it was completely abolished by bacitracin, suggesting a combined action of more than one aminopeptidase activity. Moreover, bacitracin protected most of these nonapeptide analogs from proteolysis, although it was less effective in preventing HSV R2‐(332‐337) degradation. Our results indicate that it is possible to determine, in the presence of bacitracin, the relative inhibitory potencies of HSV R2‐(329‐337) analogs with minimal error due to proteolytic susceptibility. Moreover, HSV R2‐(329‐337) modifications that were found to protect the peptide against degradation might b

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1991.tb00735.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY