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Inhibition of intercellular adhesion molecule 1-dependent biological activities by a synthetic peptide analog

Fecondo, John V. and Kent, Stephen B. H. and Boyd, Andrew W. (1991) Inhibition of intercellular adhesion molecule 1-dependent biological activities by a synthetic peptide analog. Proceedings of the National Academy of Sciences of the United States of America, 88 (7). pp. 2879-2882. ISSN 0027-8424. PMCID PMC51343. doi:10.1073/pnas.88.7.2879.

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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 µg/ml (24 µM). In addition, at a concentration of 100 µg/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.

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Additional Information:© 1991 National Academy of Sciences. Communicated by G. J. V. Nossal, December 31, 1990 (received for review November 26, 1990). We thank Karen Welch, Linda Selk, and Maureen Loudovaris for excellent technical assistance. The mass spectrometry of synthetic peptides was performed by Alun Jones. This work was supported by the Lions Fellowship, project grants from the Anti-Cancer Council of Victoria, the Victorian Health Promotion Foundation, the National Health and Medical Research Council of Australia, the Academic Development Fund, the Swinburne Institute of Technology, and funds (to S.B.H.K.) from the National Science Foundation Biological Instrumentation Division.
Funding AgencyGrant Number
Lions FellowshipUNSPECIFIED
Anti-Cancer Council of VictoriaUNSPECIFIED
Victorian Health Promotion FoundationUNSPECIFIED
National Health and Medical Research Council (NHMRC)UNSPECIFIED
Swinburne Institute of TechnologyUNSPECIFIED
Issue or Number:7
PubMed Central ID:PMC51343
Record Number:CaltechAUTHORS:20141217-075345997
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Official Citation:Inhibition of intercellular adhesion molecule 1-dependent biological activities by a synthetic peptide analog. J V Fecondo, S B Kent, and A W Boyd PNAS 1991 88 (7) 2879-2882; doi:10.1073/pnas.88.7.2879
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52931
Deposited On:17 Dec 2014 17:07
Last Modified:10 Nov 2021 19:45

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