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Conformationally constrained single‐chain peptide mimics of relaxin B‐chain secondary structure
Author(s) -
Del Borgo Mark P.,
Hughes Richard A.,
Wade John D.
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.652
Subject(s) - relaxin , chemistry , peptide , circular dichroism , protein secondary structure , pharmacophore , stereochemistry , side chain , helix (gastropod) , peptide bond , receptor , combinatorial chemistry , biochemistry , biology , organic chemistry , ecology , snail , polymer
Relaxin is a member of the insulin superfamily and has many biological actions including angiogenesis and collagen degradation. It is a 6 kDa peptide hormone consisting of two peptide chains (A and B) tethered by two disulphide bonds. Past structure–function relationship studies have shown the key receptor binding site of relaxin to be principally situated within the B‐chain α‐helix. Molecular dynamic simulations were performed to aid the design of conformationally constrained relaxin B‐chain analogues that possess α‐helical structure and relaxin‐like activity. Restraints included disulphide bonds, both single and double, and lactam bonds. Each peptide was prepared by solid phase synthesis and, following purification, subjected to detailed conformational analysis by circular dichroism spectroscopy. Of 15 prepared relaxin B‐chain mimetics, one was able to mimic the secondary structure of the native ligand as indicated by biomolecular recognition/interaction analysis using surface enhanced laser desorption ionization mass spectroscopy together with a relaxin antibody. However, none of the mimetics possess characteristic relaxin‐like biological activity which strongly indicates that the pharmacophore comprises additional structural elements other than the relaxin B‐chain α‐helix. These findings will assist in the design and preparation of novel relaxin agonists and antagonists. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.