Inhibition of intercellular adhesion molecule 1-dependent biological activities by a synthetic peptide analog.
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 micrograms/ml (24 microM). In addition, at a concentration of 100 micrograms/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.
Fecondo
J V
JV
Lions Clinical Cancer Research Laboratory, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Kent
S B
SB
Boyd
A W
AW
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D002449:Cell Aggregation / Q000187:drug effects*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D010455:Peptides; D018799:Intercellular Adhesion Molecule-1