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https://doi.org/10.5562/cca3456

Small-Molecule Interaction with G-Quadruplex DNA: Context of Anti-Cancer Drug Design

Petar M. Mitrasinovic   ORCID icon orcid.org/0000-0002-0987-4893 ; Center for Biophysical and Chemical Research, Belgrade Institute of Science and Technology, 11060 Belgrade, Serbia

Puni tekst: engleski, pdf (19 MB) str. 43-57 preuzimanja: 370* citiraj
APA 6th Edition
Mitrasinovic, P.M. (2019). Small-Molecule Interaction with G-Quadruplex DNA: Context of Anti-Cancer Drug Design. Croatica Chemica Acta, 92 (1), 43-57. https://doi.org/10.5562/cca3456
MLA 8th Edition
Mitrasinovic, Petar M.. "Small-Molecule Interaction with G-Quadruplex DNA: Context of Anti-Cancer Drug Design." Croatica Chemica Acta, vol. 92, br. 1, 2019, str. 43-57. https://doi.org/10.5562/cca3456. Citirano 24.02.2021.
Chicago 17th Edition
Mitrasinovic, Petar M.. "Small-Molecule Interaction with G-Quadruplex DNA: Context of Anti-Cancer Drug Design." Croatica Chemica Acta 92, br. 1 (2019): 43-57. https://doi.org/10.5562/cca3456
Harvard
Mitrasinovic, P.M. (2019). 'Small-Molecule Interaction with G-Quadruplex DNA: Context of Anti-Cancer Drug Design', Croatica Chemica Acta, 92(1), str. 43-57. https://doi.org/10.5562/cca3456
Vancouver
Mitrasinovic PM. Small-Molecule Interaction with G-Quadruplex DNA: Context of Anti-Cancer Drug Design. Croatica Chemica Acta [Internet]. 2019 [pristupljeno 24.02.2021.];92(1):43-57. https://doi.org/10.5562/cca3456
IEEE
P.M. Mitrasinovic, "Small-Molecule Interaction with G-Quadruplex DNA: Context of Anti-Cancer Drug Design", Croatica Chemica Acta, vol.92, br. 1, str. 43-57, 2019. [Online]. https://doi.org/10.5562/cca3456

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.

Creative Commons License 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
https://hrcak.srce.hr/217623

Posjeta: 872 *