Identification and Rational Redesign of Peptide Ligands to CRIP1, A Novel Biomarker for Cancers
View/ Open
Author
Hao, Jihua
Newton, Gail
Tassone, Gina
Wang, Zuncai
Dokholyan, Nikolay V.
Basilion, James P.
Published Version
https://doi.org/10.1371/journal.pcbi.1000138Metadata
Show full item recordCitation
Hao, Jihua, Adrian W. R. Serohijos, Gail Newton, Gina Tassone, Zuncai Wang, Dennis C. Sgroi, Nikolay V. Dokholyan, and James P. Basilion. 2008. Identification and Rational Redesign of Peptide Ligands to CRIP1, A Novel Biomarker for Cancers. PLoS Computational Biology 4(8): e1000138.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453235/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:4622131
Collections
- HMS Scholarly Articles [17917]
Contact administrator regarding this item (to report mistakes or request changes)