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The reach of linear protein-DNA dimerizers

Stafford, Ryan L. and Dervan, Peter B. (2007) The reach of linear protein-DNA dimerizers. Journal of the American Chemical Society, 129 (45). pp. 14026-14033. ISSN 0002-7863. PMCID PMC2547995. https://resolver.caltech.edu/CaltechAUTHORS:20160509-104243178

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Abstract

A protein-DNA dimerizer constructed from a DNA-binding pyrrole-imidazole polyamide and the peptide FYPWMK facilitates binding of the natural transcription factor Exd to an adjacent DNA site. Previous dimerizers have been constructed with the peptide attached to an internal pyrrole monomer in an overall branched oligomer. Linear oligomers constructed by attaching the peptide to the polyamide C-terminus expand the range of protein-DNA dimerization to six additional DNA sites. Replacing the FYPWMK hexapeptide with a WM dipeptide, which was previously functional in branched compounds, does not lead to a functional linear dimerizer. Instead, inserting an additional lysine generates a minimal, linear WMK tripeptide conjugate that maintains the activity of the larger FYPWMK dimerizers in a single DNA-binding site orientation. These studies provide insight into the importance of linker length and composition, binding site spacing and orientation, and the protein-binding domain content that are important for the optimization of protein-DNA dimerizers suitable for biological experiments.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja075247bDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja075247bPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja075247bPublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2547995/PubMed CentralArticle
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2007 American Chemical Society. Received July 13, 2007; Publication Date (Web): October 20, 2007. This work was supported by the National Institutes of Health (NIH GM51747 to P.B.D.). A fellowship from the Rose Hills Foundation (to R.L.S.) is gratefully acknowledged. We thank Drs. P. Snow and G. Hathaway (Beckman Institute, California Institute of Technology) for technical assistance with protein expression, purification, and identification.
Funders:
Funding AgencyGrant Number
NIHGM51747
Rose Hills FoundationUNSPECIFIED
Issue or Number:45
PubMed Central ID:PMC2547995
Record Number:CaltechAUTHORS:20160509-104243178
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160509-104243178
Official Citation:The Reach of Linear Protein−DNA Dimerizers Ryan L. Stafford and Peter B. Dervan Journal of the American Chemical Society 2007 129 (45), 14026-14033 DOI: 10.1021/ja075247b
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66740
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:17 May 2016 20:03
Last Modified:26 Nov 2019 11:15

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