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Design and chemical synthesis of a sequence-specific DNA-cleaving protein

Mack, David P. and Iverson, Brent L. and Dervan, Peter B. (1988) Design and chemical synthesis of a sequence-specific DNA-cleaving protein. Journal of the American Chemical Society, 110 (22). pp. 7572-7574. ISSN 0002-7863. http://resolver.caltech.edu/CaltechAUTHORS:20160511-135508947

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Abstract

We report the design and chemical synthesis of a sequence-specific DNA-cleaving protein consisting wholly of naturally occurring α-amino acids. The tripeptide, H-glyglyhis-OH (GGH), which is a consensus sequence for the copper-binding domain of serum albumin, was attached to the amino terminus of the DNA-binding domain of Hin recombinase (residues 139-190) to afford a new 55-residue protein, GGH(Hin 139-190) with two structural domains each with distinct functions, sequence-specific recognition, and cleavage of double helical DNA (Figure 1). The designed protein was synthesized by solid-phase techniques and shown, by footprinting, to be competent to bind at pM concentrations to four Hin sites, each 13 base pairs in length. In the presence of Cu(II), hydrogen peroxide, and sodium ascorbate, strong cleavage of DNA by GGH(Hin 139-190) occurs at one of the four sites by oxidative degradation of the deoxyribose backbone.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja00230a067DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja00230a067PublisherArticle
Additional Information:© 1988 American Chemical Society Received July 6, 1988. We are grateful for generous grant support from the DARPA University Research Initiative Program, an unrestricted research grant from Merck Sharp & Dohme Research Laboratories, and National Research Service Awards form the General Medical Sciences (D.P.M., B.L.I.).
Funders:
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)UNSPECIFIED
Merck Sharp & Dohme Research LaboratoriesUNSPECIFIED
NIH Predoctoral FellowshipUNSPECIFIED
Record Number:CaltechAUTHORS:20160511-135508947
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160511-135508947
Official Citation:Design and chemical synthesis of a sequence-specific DNA-cleaving protein David P. Mack, Brent L. Iverson, and Peter B. Dervan Journal of the American Chemical Society 1988 110 (22), 7572-7574 DOI: 10.1021/ja00230a067
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67002
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:19 May 2016 19:32
Last Modified:19 May 2016 19:32

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