Immunomodulatory peptides from IgSF proteins: a review.
The immunoglobulin (Ig) domain is a highly conserved domain predominantly observed in cell surface proteins due to its ability to resist proteolysis. By mutation and selection the Ig domain has evolved to serve diverse biological functions including growth and development, signaling, adhesion and protein-carbohydrate interactions. Collectively, proteins with Ig-like domain constitute the immunoglobulin superfamily (IgSF). The IgSF proteins make up over 2% of human genes constituting the largest gene family in the human genome. Analogous to the complementarity determining regions (CDR)s that form the antigen combining sites of the antibody, the high specificity of the IgSF receptor-ligand interaction is attributed to the sequence and structure of the CDR-like regions unique to each IgSF protein. Hence, CDR-like regions provide ideal templates for the design of mimetics that can potentially perturb specific IgSF receptor/ligand interactions. The determinants of binding are localized near the CDR-like regions, conformation is determined locally and is unique for each loop. In structure based drug design one of the approaches to identify lead agents is to map the receptor/ligand binding epitope onto a small peptide. Data from theoretical, structural and functional studies have been adopted in the design of novel peptide antagonists of the IgSF protein-protein interactions. Many peptide antagonists have shown significant therapeutic potential in multiple animal models. The design of the IgSF peptide analogs, rationale as therapeutic targets, functional efficacy and the clinical benefits are reviewed here.
Srinivasan
Mythily
M
Department of Oral Pathology, Indiana University School of Dentistry, Indianapolis, IN 46268, USA. mysriniv@iupui.edu
Roeske
Roger W
RW
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007136:Immunoglobulins / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D010446:Peptide Fragments; D011971:Receptors, Immunologic