Targeting E2F1–DNA complexes with microgonotropen DNA binding agents

Shu-Yuan Chiang; Thomas C Bruice; Jane C Azizkhan; Loretta Gawron; Terry A Beerman

doi:10.1073/pnas.94.7.2811

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Targeting E2F1–DNA complexes with microgonotropen DNA binding agents

Journal article

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Targeting E2F1–DNA complexes with microgonotropen DNA binding agents

Shu-Yuan Chiang, Thomas C Bruice, Jane C Azizkhan, Loretta Gawron and Terry A Beerman

Proceedings of the National Academy of Sciences - PNAS, v 94(7), pp 2811-2816

01 Apr 1997

DOI: https://doi.org/10.1073/pnas.94.7.2811

PMID: 9096302

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Abstract

Biological Sciences

Microgonotropen (MGT) DNA binding drugs, which consist of an A+T-selective DNA minor groove binding tripyrrole peptide and polyamine chains attached to a central pyrrole that extend drug contact into the DNA major groove, were found to be extraordinarily effective inhibitors of E2 factor 1 (E2F1) association with its DNA promoter element (5′-TTTCGCGCCAAA). The most active of these drugs, MGT-6a, was three orders of magnitude more effective than distamycin and inhibited complexes between E2F1 and the dihydrofolate reductase promoter by 50% at 0.00085 μM. A relationship was found between the measured equilibrium constants for binding of MGTs to the A+T region of d(GGCGA 3 T 3 GGC)/d(CCGCT 3 A 3 CCG) and their inhibition of complex formation between E2F1 and the DNA promoter element. A representative of the potent MGT inhibitors was significantly more active on inhibition of E2F1–DNA complex formation compared with disruption of a preexisting complex.

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Details

Title: Targeting E2F1–DNA complexes with microgonotropen DNA binding agents
Creators: Shu-Yuan Chiang - Experimental Therapeutics Department, Roswell Park Cancer Institute, Buffalo, NY 14263; and
Thomas C Bruice - Experimental Therapeutics Department, Roswell Park Cancer Institute, Buffalo, NY 14263; and
Jane C Azizkhan - Experimental Therapeutics Department, Roswell Park Cancer Institute, Buffalo, NY 14263; and
Loretta Gawron - Experimental Therapeutics Department, Roswell Park Cancer Institute, Buffalo, NY 14263; and
Terry A Beerman - Experimental Therapeutics Department, Roswell Park Cancer Institute, Buffalo, NY 14263; and
Publication Details: Proceedings of the National Academy of Sciences - PNAS, v 94(7), pp 2811-2816
Publisher: The National Academy of Sciences of the USA
Resource Type: Journal article
Language: English
Academic Unit: Biochemistry and Molecular Biology
Web of Science ID: WOS:A1997WR93000014
Scopus ID: 2-s2.0-0030961783
Other Identifier: 991014877810304721

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Collaboration types: Domestic collaboration
Web of Science research areas: Biochemistry & Molecular Biology