Croatica Chemica Acta, Vol. 92 No. 1, 2019.
Izvorni znanstveni članak
https://doi.org/10.5562/cca3456
Small-Molecule Interaction with G-Quadruplex DNA: Context of Anti-Cancer Drug Design
Petar M. Mitrasinovic
orcid.org/0000-0002-0987-4893
; Center for Biophysical and Chemical Research, Belgrade Institute of Science and Technology, 11060 Belgrade, Serbia
Sažetak
Targeting G-quadruplex (G4) DNA structures by small molecules is a potential strategy for directing gene therapy of cancer disease. Herein, novel insights into non-covalent interactions between a structurally diversified spectrum of ligands and a G-quadruplex DNA (formed in the c-Myc oncogene promoter region) are reported. Solvation-induced effects on and entropic contributions to the binding free energy are explored. In addition, the correlation of G4 domain motions and active site rearrangements with the binding of highest affinity ligands, being associated with the fundamentally distinguishable modes of interaction (external stacking: BRACO-19, TMPyP4, and CX-3543; groove binding: Sanguinarine, Tetrahydropalmatine, and Hoechst 33258), is quantitatively evaluated and elaborated by observing thermodynamic consequences of the receptor conformational flexibility changes in the asymptotic regime (t → ∞) of molecular dynamics (MD) simulation. BRACO-19 and Tetrahydropalmatine are identified as unique (thermodynamically favorable and highly selective) G4-DNA binders. Implications of the present study for experimental research are elucidated.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Ključne riječi
anti-cancer drug design; BRACO-19; c-Myc oncogene promoter; G-quadruplex DNA; molecular dynamics; Tetrahydropalmatine
Hrčak ID:
217623
URI
Datum izdavanja:
28.1.2019.
Posjeta: 2.981 *