INHIBITION OF INTERCELLULAR-ADHESION MOLECULE 1-DEPENDENT BIOLOGICAL-ACTIVITIES BY A SYNTHETIC PEPTIDE ANALOG
Details
Publication Year 1991-04,Volume 88,Issue #7,Page 2879-2882
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type
Journal Article
Abstract
We have used a combination of hydropathy analysis of the intercellular adhesion molecule 1 (ICAM-1) sequence and dot-matrix comparison of the sequence with the homologous, but functionally distinct, protein myelin-associated glycoprotein to identify a putative functional binding region. One polar, and presumably surface-exposed, region of ICAM-1 showed no significant identity with myelin-associated glycoprotein. A synthetic peptide analog based on the sequence of this region (JF9) mimicked the inhibitory effects of the anti-ICAM-1 monoclonal antibody WEHI-CAM-1. These included inhibition of ICAM-1-dependent homotypic aggregation of Raji Burkitt lymphoma and phorbol-ester treated U937 cells at concentrations as low as 80-mu-g/ml (24-mu-M). In addition, at a concentration of 100-mu-g/ml, the peptide analog effectively inhibited cytotoxic cell activity, an ICAM-1-dependent effector function of the immune response. This simple method of sequence analysis may have general applicability to the identification of functional domains in homologous, but functionally distinct, proteins such as the translated products of gene families.
Publisher
NATL ACAD SCIENCES
Keywords
ANTIGEN-1 LFA-1; ICAM-1; LIGAND; RECEPTOR; CELLS; IMMUNOGLOBULIN; RECOGNITION; MECHANISMS; SEQUENCES; PROTEIN
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Creation Date: 1991-04-01 12:00:00
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