A peptide mimetic of an anti-CD4 monoclonal antibody by rational design |
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Authors: | Casset Florence Roux Florence Mouchet Patrick Bes Cedric Chardes Thierry Granier Claude Mani Jean-Claude Pugnière Martine Laune Daniel Pau Bernard Kaczorek Michel Lahana Roger Rees Anthony |
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Affiliation: | Synt:em, Parc Scientifique Georges Besse, FR-30035 1, Ni;mes Cédex, France. |
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Abstract: | The development of rational methods to design 'continuous' sequence mimetics of discontinuous regions of protein sequence has, to now, been only marginally successful. This has been largely due to the difficulty of constraining the recognition elements of a mimetic structure to the relative conformational and spatial orientations present in the parent molecule. Using peptide mapping to determine 'active' antigen recognition residues, molecular modeling, and a molecular dynamics trajectory analysis, we have developed a peptide mimic of an anti-CD4 antibody, containing antigen contact residues from multiple CDRs. The design described is a 27-residue peptide formed by juxtaposition of residues from 5 CDR regions. It displays an affinity for the antigen (CD4) of 0.9nM, compared to 2nM for the parent antibody ST40. Nevertheless, the mimetic shows low biological activity in an anti-retroviral assay. |
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Keywords: | Antibody modeling Antibody mimetic Paratope mimetic Rational design Anti-CD4 monoclonal antibody ST40 |
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