Dual surface selection methodology for the identification of thrombin binding epitopes from hotspot biased phage-display libraries

Srivats Rajagopal, Roberto Meza-Romero, Indraneel Ghosh

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Protein libraries biased towards amino-acid residues found at so-called 'hotspots' were incorporated into the beta-sheet region of the thermostable variant (HTB1) of the B1 domain of the immunoglobulin (IgG) binding protein G and expressed as gene 3 fusions on M13 bacteriophage. The HTB1 library (2.2×109) variants with a minimal 12 amino acid basis set were selected for binding IgG, to ensure structural conservation, and subsequently to thrombin to evolve a thrombin-binding function. We believe that this dual surface selection strategy will have great utility in evolving new bi-functional proteins without compromising structure. Furthermore the discrete beta-sheet epitopes identified by our methodology will lend itself to small-molecule mimicry of beta-sheets.

Original languageEnglish (US)
Pages (from-to)1389-1393
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number6
DOIs
StatePublished - Mar 22 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Dual surface selection methodology for the identification of thrombin binding epitopes from hotspot biased phage-display libraries'. Together they form a unique fingerprint.

  • Cite this