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Transfer of a protein binding epitope to a minimal designed peptide
Author(s) -
Quan C.,
Skelton N. J.,
Clark K.,
Jackson D. Y.,
Renz M. E.,
Chiu H. H.,
Keating S. M.,
Beresini M. H.,
Fong S.,
Artis D. R.
Publication year - 1998
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(1998)47:4<265::aid-bip2>3.0.co;2-k
Subject(s) - epitope , chemistry , peptide , integrin , mutant , mutagenesis , protein structure , linear epitope , biochemistry , peptide sequence , antigen , cell , biology , genetics , gene
Abstract Results from protein mutagenesis and x‐ray crystallographic studies of the multidomain protein Vascular Cell Adhesion Molecule (VCAM) were used to design cyclic octapeptides that retain the critical structural and binding elements of the epitope of VCAM in the interaction with the integrin α 4 β 1 (VLA‐4). Changes in the activities of peptide analogues correlated with the relative activities of protein mutants of VCAM, and predicted the properties of two new mutants that bound α 4 β 1 with improved affinity vs wild type protein. The nmr structures of two peptides revealed a high degree of similarity to the structure of the VCAM binding epitope. These results demonstrate that a compact binding epitope identified via protein structure–function studies may be transferred to a synthetically accessible small peptide with the key structure–activity relationships intact. © 1998 John Wiley & Sons, Inc. Biopoly 47: 265–275, 1998