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

Casset F,Roux F,Mouchet P,Bes C,Chardes T,Granier C,Mani JC,Pugnière M,Laune D,Pau B,Kaczorek M,Lahana R,Rees A

doi

10.1016/s0006-291x(03)01131-8

subject

Has Abstract

pub_date

2003-07-18 00:00:00

pages

198-205

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006291X03011318

journal_volume

307

pub_type

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