title: A peptide mimetic of an anti-CD4 monoclonal antibody by rational design.
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.
authors.affiliation: Synt:em, Parc Scientifique Georges Besse, FR-30035 1, Ni;mes Cédex, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Casset
authors.forename: Florence
authors.initials: F
authors.lastname: Roux
authors.forename: Patrick
authors.initials: P
authors.lastname: Mouchet
authors.forename: Cedric
authors.initials: C
authors.lastname: Bes
authors.forename: Thierry
authors.initials: T
authors.lastname: Chardes
authors.forename: Claude
authors.initials: C
authors.lastname: Granier
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mani
authors.forename: Martine
authors.initials: M
authors.lastname: Pugnière
authors.forename: Daniel
authors.initials: D
authors.lastname: Laune
authors.forename: Bernard
authors.initials: B
authors.lastname: Pau
authors.forename: Michel
authors.initials: M
authors.lastname: Kaczorek
authors.forename: Roger
authors.initials: R
authors.lastname: Lahana
authors.forename: Anthony
authors.initials: A
authors.lastname: Rees
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D010455:Peptides