Transfer of a protein binding epitope to a minimal designed peptide

Autor:	C, Quan, N J, Skelton, K, Clark, D Y, Jackson, M E, Renz, H H, Chiu, S M, Keating, M H, Beresini, S, Fong, D R, Artis
Rok vydání:	1999
Předmět:	Models Molecular Integrins Binding Sites Magnetic Resonance Spectroscopy Receptors Lymphocyte Homing Vascular Cell Adhesion Molecule-1 Integrin alpha4beta1 Binding Competitive Peptides Cyclic Peptide Fragments Epitopes Structure-Activity Relationship Methotrexate Protein Binding
Zdroj:	Biopolymers. 47(4)
ISSN:	0006-3525
Popis:	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 alpha 4 beta 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 alpha 4 beta 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::15e4fdc4dd917acaf15b4ac91aa42c71 https://pubmed.ncbi.nlm.nih.gov/10036968 Zobrazit plný text záznamu Plný text