Improving the affinity of antigens for mutated antibodies by use of statistical molecular design

Journal of Peptide Science : an Official Publication of the European Peptide Society
Ilona MandrikaJarl E S Wikberg

Abstract

We demonstrate the use of statistical molecular design (SMD) in the selection of peptide libraries aimed to systematically investigate antigen-antibody binding spaces. Earlier, we derived two novel antibodies by mutating the complementarity-determining region of the anti-p24 (HIV-1) single chain Fv antibody, CB4-1 that had lost their affinity for a p24 epitope-homologous peptide by 8- and 60-fold. The present study was devoted to explore how peptide libraries can be designed under experimental design criteria for effective screening of peptide antigens. Several small peptide-antigen libraries were selected using SMD principles and their activities were evaluated by their binding to SPOT-synthesized peptide membranes and by fluorescence polarization (FP). The approach was able to reveal the most critical residues required for antigen binding, and finally to increase the binding activity by proper modifications of amino acids in the peptide antigen. A model of the active peptide binding pocket formed by the mutated scFv and the antigen was compatible with the information gained from the experimental data. Our results suggest that SMD approaches can be used to explore peptide antigen features essential for their interactions with ...Continue Reading

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Aug 20, 1987·Journal of Molecular Biology·C Chothia, A M Lesk
Jan 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·B C Braden, R J Poljak
Oct 1, 1996·Molecular Diversity·J R AppelC Pinilla
Jul 14, 1998·Immunotechnology : an International Journal of Immunological Engineering·H R HoogenboomR C Roovers
Jul 30, 1999·Molecular Diversity·A LinussonB Nordén
Jan 29, 2000·Journal of Immunological Methods·C SchaffitzelA Plückthun
Feb 7, 2001·Journal of Medicinal Chemistry·A LinussonS Wold
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·K WinklerW Höhne
Jul 27, 2001·Combinatorial Chemistry & High Throughput Screening·M H Van Regenmortel, L Choulier
May 30, 2002·Protein Engineering·Laurence ChoulierDanièle Altschuh
Jun 6, 2002·The Journal of Biological Chemistry·Erwin De GenstKarl Andersson
Jul 24, 2002·Journal of Immunological Methods·Ulrich ReinekeJens Schneider-Mergener
Apr 11, 2007·Journal of Molecular Recognition : JMR·Ilona MandrikaJarl E S Wikberg

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Citations

May 14, 2009·Chembiochem : a European Journal of Chemical Biology·Rudolf Volkmer

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