uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Improving the affinity of antigens for mutated antibodies by use of statistical molecular design
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Pharmacology. (Proteochemometric group)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Pharmacology. (Proteochemometric group)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Pharmacology. (Proteochemometric group)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Pharmacology. (Proteochemometric group)
Show others and affiliations
2008 (English)In: Journal of Peptide Science, ISSN 1075-2617, Vol. 14, no 7, 786-96 p.Article in journal (Refereed) Published
Abstract [en]

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 antibodies.

Place, publisher, year, edition, pages
2008. Vol. 14, no 7, 786-96 p.
Keyword [en]
single chain antibody, mutagenesis, peptide antigen, SPOT synthesis, fluorescence polarization, statistical molecular design
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-104219DOI: 10.1002/psc.999ISI: 000257725000002PubMedID: 18200617OAI: oai:DiVA.org:uu-104219DiVA: diva2:219547
Available from: 2009-05-27 Created: 2009-05-27 Last updated: 2009-10-19Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Pharmaceutical Pharmacology
In the same journal
Journal of Peptide Science
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 434 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf