Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5557
pubmed:dateCreated
2002-2-8
pubmed:abstractText
The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1095-9203
pubmed:author
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1086-9
pubmed:dateRevised
2007-3-19
pubmed:meshHeading
pubmed-meshheading:11834839-Amino Acid Sequence, pubmed-meshheading:11834839-Animals, pubmed-meshheading:11834839-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:11834839-Cyclosporine, pubmed-meshheading:11834839-Dermatitis, Irritant, pubmed-meshheading:11834839-Dinitrofluorobenzene, pubmed-meshheading:11834839-Drug Design, pubmed-meshheading:11834839-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:11834839-Epitopes, pubmed-meshheading:11834839-Female, pubmed-meshheading:11834839-Humans, pubmed-meshheading:11834839-Immunoglobulin Fab Fragments, pubmed-meshheading:11834839-Immunosuppressive Agents, pubmed-meshheading:11834839-Intercellular Adhesion Molecule-1, pubmed-meshheading:11834839-Lymphocyte Culture Test, Mixed, pubmed-meshheading:11834839-Lymphocyte Function-Associated Antigen-1, pubmed-meshheading:11834839-Mice, pubmed-meshheading:11834839-Mice, Inbred BALB C, pubmed-meshheading:11834839-Molecular Mimicry, pubmed-meshheading:11834839-Mutagenesis, pubmed-meshheading:11834839-Protein Structure, Secondary, pubmed-meshheading:11834839-Structure-Activity Relationship, pubmed-meshheading:11834839-Thiophenes, pubmed-meshheading:11834839-beta-Alanine
pubmed:year
2002
pubmed:articleTitle
Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule.
pubmed:affiliation
Department of Bioorganic Chemistry, Genentech, One DNA Way, South San Francisco, CA 94080, USA. trg@gene.com
pubmed:publicationType
Journal Article