Receptor-bound conformation of an alpha(5)beta(1) integrin antagonist by (15)N-edited 2D transferred nuclear overhauser effects.
We report the results of (15)N-edited 2D transferred NOE experiments of the partially (15)N-labeled alpha(5)beta(1) antagonist c[Mpa(15)N-Arg-(15)N-Gly-(15)N-Asp-(15)N-Asp-(15)N-Val-Cys]-NH(2) (Mpa denotes mercaptopropionic acid) in the presence of the native alpha(5)beta(1) receptor. The alpha(5)beta(1) integrin receptor is believed to be involved in tumor metastasis and the rational design of alpha(5)beta(1) integrin antagonist is therefore of considerable interest. Our experiments provide insight into the alpha(5)beta(1) receptor-bound conformation of the antagonist c[MpaRGDDVC]-NH2 and will be important for the design of novel antagonists.
Zhang
Li
L
Department of Chemistry and Biochemistry, University of California at San Diego, 6223 Pacific Hall, La Jolla, CA 92093-0343, USA.
Mattern
Ralph-Heiko
RH
Malaney
Timothy I
TI
Pierschbacher
Michael D
MD
Goodman
Murray
M
D000818:Animals; D005260:Female; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D010920:Placenta / Q000737:chemistry; D011487:Protein Conformation; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D009587:Nitrogen Isotopes; D009842:Oligopeptides; D017469:Receptors, Fibronectin; C047981:arginyl-glycyl-aspartic acid