ISSN:0570-0833    

DOI:10.1002/anie.199414071

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractChanges in the conformation of the units within the peptide chain are the elementary processes in the folding of a protein into its native three‐dimensional structure. Even a few years ago protein folding in vivo was considered to be an autonomous process not requiring the help of enzymes or auxiliary substances. Recently an increasing number of proteins that assist in the folding process have been found; these include enzymes that catalyze conformational interconversions. Thecis/transisomerization of the petptide bond N‐terminal to a praline residue is catalyzed by peptidyl‐prolylcis/transisomerases (PPIases). Two families of these ubiquitous and phylogenetically highly conserved enzymes are known, the cyclophilins and FK506‐binding proteins. Their catalytic activity is extremely highmdash;the rate constants for the bimolecular reactions they catalyze approach the diffusion‐controlled limit for enzyme‐substrate reactions. These enzymes increase the rate of isomerization in oligopeptides as well as in intermediate in protein folding. It is not yet known which structural units in the cell serve as substrates and exactly which reactions are catalyzed. However, these isomerases have been shown to interact with the heat shock proteins of the nonactivated steroid receptors and with the gag polyprotein of the AIDS HIV‐1 virus. The immunosuppressive agents cyclosporine A and FK506 are highly effective inhibitors for PPIases. Surprisingly these compounds affect the signal cascade of T cells but not through enzyme inhibition; the inhibitor‐enzyme complexes themselves are the active agents. These complexes exhibit properties not displayed by the individual components and thus are able to affect other cellular components. The current model of the suppression of the antigen‐ and mitogen‐stimulated clonal expansion of T cell

ISSN:0570-0833    

DOI:10.1002/anie.199414151

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

摘要:

AbstractThe molecular basis o taste has been extensively studied over many years. The research carried out in our laboratories is focused on the elucidation of detailed structure–taste relationships of peptides and peptidomimetics using an “integrated” approach employing synthesis, analysis of NMR spectra, computer simulations, and X‐ray crystallography. Various peptidomimetic residues have been incorporated to introduce predictable structural constraints into taste ligands. These constraints eliminate some of the molecular flexibility and allow us to develop structure–activity relationships. We describe here the topochemical requirements of the sweet and bitter taste receptor(s) and develop detailed structure‐taste relationships with considerable predictive power for peptides and relate

ISSN:0570-0833    

DOI:10.1002/anie.199414371

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199414521

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199414551

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199414571

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199414581

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199414591

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199414621

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY

ISSN:0570-0833    

DOI:10.1002/anie.199414631

出版商:Hüthig&Wepf Verlag    

年代:1994

数据来源: WILEY