A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system is a cell cycle inhibitor.

Published

Journal Article

Peptides or small molecules able to modulate protein-protein interactions hold promise as tools with which to probe and manipulate biological pathways. An important issue in this nascent field is to evaluate different methods with which to search libraries for molecules that modulate the function of specific target proteins. One strategy is to screen libraries for molecules that bind specifically to a protein known to be critical in the pathway of interest, with the expectation that the molecules isolated will recognize regions of the target protein important for its function and thereby exhibit biological activity. Here, a peptide library was screened using a two-hybrid-like system for molecules able to bind human CDC6 protein (CDC6p), required for the initiation of DNA replication in eukaryotic cells. From a collection of over a million peptides, a single species that exhibited good affinity and specificity for binding CDC6p was obtained. When expressed in human cells, the peptide inhibited cell cycle progression and exhibited other properties expected of a CDC6p inhibitor. This approach, which does not require detailed knowledge of the mechanism of action of a protein target, may be generally useful for isolating peptides capable of manipulating biological pathways.

Full Text

Duke Authors

Cited Authors

  • Zhu, W; Williams, RS; Kodadek, T

Published Date

  • October 2000

Published In

Volume / Issue

  • 275 / 41

Start / End Page

  • 32098 - 32105

PubMed ID

  • 10896933

Pubmed Central ID

  • 10896933

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.m001560200

Language

  • eng