Development of biologically active peptides based on antibody structure.
Antibody molecules are composed of several functional domains, including a variable domain that contacts antigen and a constant domain. The hypervariable regions of antibody molecules play an integral role in determining their specificity. However, the delineation of specific residues most critical in binding is difficult. We have been studying a monoclonal antibody (87.92.6) that binds to the reovirus type 3 receptor on a number of cell types, down-modulates the receptor, and inhibits DNA synthesis in the cells. We have shown that a peptide derived from the second complementarity-determining region of the monoclonal antibody 87.92.6 light-chain variable region can reproduce both of these effects. We were also able to demonstrate specific amino acid residues and structural features involved in producing these effects. The study of antibody structure, coupled with molecular synthetic techniques, can lead to the development of biologically active substances with potential clinical use.
Williams
W V
WV
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Moss
D A
DA
Kieber-Emmons
T
T
Cohen
J A
JA
Myers
J N
JN
Weiner
D B
DB
Greene
M I
MI
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003208:Concanavalin A; D005260:Female; D007147:Immunoglobulin Light Chains / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D012089:Mammalian orthoreovirus 3 / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D011487:Protein Conformation; D011991:Receptors, Virus / Q000276:immunology* / Q000502:physiology; D012087:Reoviridae / Q000276:immunology*; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D010455:Peptides; D011991:Receptors, Virus; D003208:Concanavalin A