Identification and validation of human DNA ligase inhibitors using computer-aided drug design.

Identification and validation of human DNA ligase inhibitors using computer-aided drug design. Research Abstract Details 

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Identification and validation of human DNA ligase inhibitors using computer-aided drug design. Abstract Text:

Linking together of DNA strands by DNA ligases is essential for DNA replication and repair. Since many therapies used to treat cancer act by causing DNA damage, there is growing interest in the development of DNA repair inhibitors. Accordingly, virtual database screening and experimental evaluation were applied to identify inhibitors of human DNA ligase I (hLigI). When a DNA binding site within the DNA binding domain (DBD) of hLigI was targeted, more than 1 million compounds were screened from which 192 were chosen for experimental evaluation. In DNA joining assays, 10 compounds specifically inhibited hLigI, 5 of which also inhibited the proliferation of cultured human cell lines. Analysis of the 10 active compounds revealed the utility of including multiple protein conformations and chemical clustering in the virtual screening procedure. The identified ligase inhibitors are structurally diverse and have druglike physical and molecular characteristics making them ideal for further drug development studies.

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Identification and validation of human DNA ligase inhibitors using computer-aided drug design. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of medicinal chemistry

VOLUME: 51

Page Numbers: 4553-62

Journal Abbreviation: J. Med. Chem.

ISSN: 1520-4804

DAY: 17

MONTH: 07

YEAR: 2008

Identification and validation of human DNA ligase inhibitors using computer-aided drug design. Information

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LANGUAGE: eng

NlmUniqueID: 9716531

Identification and validation of human DNA ligase inhibitors using computer-aided drug design. Keywords Mesh Terms:

KEYWORDS: Substrate Specificity

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Identification and validation of human DNA ligase inhibitors using computer-aided drug design. Information

Substance Name: DNA Ligases

Registry Number: EC 6.5.1.-

Grant and Affiliation Information for Identification and validation of human DNA ligase inhibitors using computer-aided drug design.

AFFILIATION: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM57479

ACRONYM: GM

MEDLINETA: J Med Chem

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