Simian Virus 40 Large T-Antigen G-Quadruplex DNA Helicase Inhibition by G-Quadruplex DNA-Interactive Agents.

Simian Virus 40 Large T-Antigen G-Quadruplex DNA Helicase Inhibition by G-Quadruplex DNA-Interactive Agents. Research Abstract Details 

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Simian Virus 40 Large T-Antigen G-Quadruplex DNA Helicase Inhibition by G-Quadruplex DNA-Interactive Agents. Abstract Text:

Bodin Tuesuwan,Jonathan T Kern,Pei Wang Thomas,Mireya Rodriguez,Jing Li,Wendi M David,Sean M Kerwin,

On the basis of growing evidence for G-quadruplex DNA structures in genomic DNA and the presumed need to resolve these structures for DNA replication, the G-quadruplex DNA unwinding ability of a prototypical replicative helicase, SV40 large T-antigen (T-ag), was investigated. Here, we demonstrate that this G-quadruplex helicase activity is robust and comparable to the duplex helicase activity of T-ag. Analysis of the SV40 genome demonstrates the presence of sequences that may form intramolecular G-quadruplexes, which are the presumed natural substrates for the G-quadruplex helicase activity of T-ag. A number of G-quadruplex-interactive agents as well as new perylene diimide (PDI) derivatives have been investigated as inhibitors of both the G-quadruplex and the duplex DNA helicase activities of T-ag. A unique subset of these G-quadruplex-interactive agents inhibits the G-quadruplex DNA unwinding activity of T-ag, relative to those reported to inhibit G-quadruplex DNA unwinding by RecQ-family helicases. We also find that certain PDIs are both potent and selective inhibitors of the G-quadruplex DNA helicase activity of T-ag. Surface plasmon resonance and fluorescence spectroscopic G-quadruplex DNA binding studies of these T-ag G-quadruplex helicase inhibitors have been carried out, demonstrating the importance of attributes in addition to binding affinity for G-quadruplex DNA that may be important for inhibition. The identification of potent and selective inhibitors of the G-quadruplex helicase activity of T-ag provides tools for probing the specific role of this activity in SV40 replication.

Simian Virus 40 Large T-Antigen G-Quadruplex DNA Helicase Inhibition by G-Quadruplex DNA-Interactive Agents. Publishing Authors By Initials

B Tuesuwan,JT Kern,PW Thomas,M Rodriguez,J Li,WM David,SM Kerwin,

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Simian Virus 40 Large T-Antigen G-Quadruplex DNA Helicase Inhibition by G-Quadruplex DNA-Interactive Agents. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochemistry

VOLUME: 47

Page Numbers: 1896-909

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 19

MONTH: 01

YEAR: 2008

Simian Virus 40 Large T-Antigen G-Quadruplex DNA Helicase Inhibition by G-Quadruplex DNA-Interactive Agents. Information

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LANGUAGE: eng

NlmUniqueID: 370623

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Grant and Affiliation Information for Simian Virus 40 Large T-Antigen G-Quadruplex DNA Helicase Inhibition by G-Quadruplex DNA-Interactive Agents.

AFFILIATION: Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, and Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas 78666.

Country: United States

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MEDLINETA: Biochemistry

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