Journal
CHEMMEDCHEM
Volume 9, Issue 5, Pages 899-911Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201300566
Keywords
drug design; G-Quadruplexes; interaction diversity; ligand effects; polymorphism
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Funding
- Program for Zhejiang Leading Team of Science and Technology Innovation [2011R50021]
- Zhejiang provincial Natural Science Foundation of China [LY12B02019]
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G-Quadruplexes are distinct nucleic acid secondary structures that are formed from G-rich DNA and RNA sequences; they are built around successive G-tetrads of Hoogsteen hydrogen-bonded guanine bases. The existence of G-quadruplex structures has been confirmed in the human telomere and genome, and their biological functions have been demonstrated. Thus, the prospect of using G-quadruplex structures as a novel target for drug design is important. This review focuses on structural polymorphism of G-quadruplexes on the basis of the classification of the strand number of the G-quadruplex formed and its interaction diversity with small molecules (G4-ligands) that display high affinity and, more importantly, selectivity. Also, we outlook some future challenges for G-quadruplex structure and ligand studies. Such information, together with the biological functions of for G-quadruplex, will be of crucial importance for the research and development of drugs that target G-quadruplexes formed from particular genes and human telomeres.
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