Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 118, Issue -, Pages 629-639Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2018.06.115
Keywords
VEGF G-quadruplex DNA; Kaempferol; Morin; Spectroscopy; Molecular docking; Preferential binding
Funding
- Department of Science and Technology (DST), Govt. of India [DST INSPIRE Grant] [DST/INSPIRE/04/2014/000217]
- Kempe foundations [SMK-1632.2]
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G-quadruplex (G4) structures are known to be promising anticancer drug targets and flavonols (an important class of fiavonoids) are small molecules reported to possess several health-promoting properties including those of anticancer activities. In this work, we explored the interactions of the structurally related plant flavonols kaempferol (KAE; 3,5,7,4'-OH flavone) and morin (MOR; 3,5,7,2',4'-OH flavone) with various G4-DNA sequences along with duplex DNA using a combination of spectroscopic and molecular docking studies. Our results revealed that KAE shows preferential interaction with VEGF G4-DNA in comparison to the other G4 sequences and duplex DNA. Moreover, KAE enhances the thermal stability of VEGF G4-DNA. In contrast, MOR exhibits an appreciably weaker level of interaction with both duplex and various G4-DNAs, with no significant structural specificity. The contrasting DNA binding behaviors suggest a crucial role of the 2'-OH substituent in the Bring of flavonol moiety. While KAE is relatively planar, MOR adopts a significantly non-planar conformation attributable to steric hindrance from the additional 2'-OH substituent. This small structural difference is apparently very important for the ability of KAE and MOR to interact with VEGF G4-DNA. Thus, KAE (but not MOR) appears to be an effective ligand for VEGF G4-DNA, opening up possibilities of its application for regulation of gene expression in cancer cells. (C) 2018 Elsevier B.V. All rights reserved.
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