Inhibition of intercellular adhesion molecule 1-dependent biological activities by a synthetic peptide analog
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 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.
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.Attached Files
Published - PNAS-1991-Fecondo-2879-82.pdf
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Additional details
- PMCID
- PMC51343
- Eprint ID
- 52931
- Resolver ID
- CaltechAUTHORS:20141217-075345997
- Lions Fellowship
- Anti-Cancer Council of Victoria
- Victorian Health Promotion Foundation
- National Health and Medical Research Council (NHMRC)
- Swinburne Institute of Technology
- NSF
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2014-12-17Created from EPrint's datestamp field
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2021-11-10Created from EPrint's last_modified field