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

Publication ,  Journal Article
Zhu, W; Williams, RS; Kodadek, T
Published in: J Biol Chem
October 13, 2000

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.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 13, 2000

Volume

275

Issue

41

Start / End Page

32098 / 32105

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Transfection
  • Substrate Specificity
  • S Phase
  • Protein Binding
  • Peptides
  • Peptide Library
  • Nuclear Proteins
  • Molecular Sequence Data
  • Microscopy, Fluorescence
 

Citation

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Zhu, W., Williams, R. S., & Kodadek, T. (2000). A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system is a cell cycle inhibitor. J Biol Chem, 275(41), 32098–32105. https://doi.org/10.1074/jbc.M001560200
Zhu, W., R. S. Williams, and T. Kodadek. “A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system is a cell cycle inhibitor.J Biol Chem 275, no. 41 (October 13, 2000): 32098–105. https://doi.org/10.1074/jbc.M001560200.
Zhu W, Williams RS, Kodadek T. A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system is a cell cycle inhibitor. J Biol Chem. 2000 Oct 13;275(41):32098–105.
Zhu, W., et al. “A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system is a cell cycle inhibitor.J Biol Chem, vol. 275, no. 41, Oct. 2000, pp. 32098–105. Pubmed, doi:10.1074/jbc.M001560200.
Zhu W, Williams RS, Kodadek T. A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system is a cell cycle inhibitor. J Biol Chem. 2000 Oct 13;275(41):32098–32105.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 13, 2000

Volume

275

Issue

41

Start / End Page

32098 / 32105

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Transfection
  • Substrate Specificity
  • S Phase
  • Protein Binding
  • Peptides
  • Peptide Library
  • Nuclear Proteins
  • Molecular Sequence Data
  • Microscopy, Fluorescence