Identification and rational redesign of peptide ligands to CRIP1, a novel biomarker for cancers

Jihua Hao, Adrian W.R. Serohijos, Gail Newton, Gina Tassone, Zuncai Wang, Dennis C. Sgroi, Nikolay V. Dokholyan, James P. Basilion

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Cysteine-rich intestinal protein 1 (CRIP1) has been identified as a novel marker for early detection of cancers. Here we report on the use of phage display in combination with molecular modeling to identify a high-affinity ligand for CRIP1. Panning experiments using a circularized C7C phage library yielded several consensus sequences with modest binding affinities to purified CRIP1. Two sequence motifs, A1 and B5, having the highest affinities for CRIP1, were chosen for further study. With peptide structure information and the NMR structure of CRIP1, the higher-affinity A1 peptide was computationally redesigned, yielding a novel peptide, A1M, whose affinity was predicted to be much improved. Synthesis of the peptide and saturation and competitive binding studies demonstrated approximately a 10-28-fold improvement in the affinity of A1M compared to that of either A1 or B5 peptide. These techniques have broad application to the design of novel ligand peptides.

Original languageEnglish (US)
Article numbere1000138
JournalPLoS computational biology
Volume4
Issue number8
DOIs
StatePublished - Aug 2008

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

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