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Med Res Rev. 2013 Sep;33(5):1119-73. doi: 10.1002/med.21278. Epub 2013 Apr 30.

Structure-based DNA-targeting strategies with small molecule ligands for drug discovery.

Author information

1
Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA.

Abstract

Nucleic acids are the molecular targets of many clinical anticancer drugs. However, compared with proteins, nucleic acids have traditionally attracted much less attention as drug targets in structure-based drug design, partially because limited structural information of nucleic acids complexed with potential drugs is available. Over the past several years, enormous progresses in nucleic acid crystallization, heavy-atom derivatization, phasing, and structural biology have been made. Many complicated nucleic acid structures have been determined, providing new insights into the molecular functions and interactions of nucleic acids, especially DNAs complexed with small molecule ligands. Thus, opportunities have been created to further discover nucleic acid-targeting drugs for disease treatments. This review focuses on the structure studies of DNAs complexed with small molecule ligands for discovering lead compounds, drug candidates, and/or therapeutics.

KEYWORDS:

modification and derivatization; nucleic acids; small molecule ligands; structure-based drug discovery; structures of DNA-ligand complexes

PMID:
23633219
PMCID:
PMC3954796
DOI:
10.1002/med.21278
[Indexed for MEDLINE]
Free PMC Article

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