Alkaloid Escholidine and Its Interaction with DNA Structures

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Publikace nespadá pod Fakultu sportovních studií, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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JAROŠOVÁ Petra HANNIG Pavel KOLKOVÁ Kateřina MAZZINI Stefania TÁBORSKÁ Eva GARGALLO Raimundo BORGONOVO Gigliola ARTALI Roberto TÁBORSKÝ Petr

Rok publikování 2021
Druh Článek v odborném periodiku
Časopis / Zdroj BIOLOGY-BASEL
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://www.mdpi.com/2079-7737/10/12/1225
Doi http://dx.doi.org/10.3390/biology10121225
Klíčová slova escholidine; G-quadruplex; DNA; cancer; alkaloid; spectroscopy
Popis Simple Summary Escholidine is a rare protoberberine alkaloid present in trace amounts in roots of Eschscholtzia californica and in the aerial parts of Hunnemannia fumariaefolia. Due to the characteristic charged structure, it can interact with various forms of nucleic acids, including non-canonical structures. A series of spectroscopic experiments have shown notable melting stabilization of antiparallel G-quadruplex sequence DL40 induced by escholidine (Delta T-m = 5.2 degrees C). Interaction stoichiometry calculated from fluorescence titration curves was estimated to be 4:1 or 5:1 (alkaloid:DNA). Nuclear Magnetic Resonance (NMR) experiments have confirmed that an external loop binding is likely responsible for this stabilization. The three-dimensional model of the complex between escholidine and DL40, obtained as a result of the molecular docking experiment, implies the preferred orientation of escholidine to the quadruplex structure. Since the stabilization of telomeric G-quadruplex structures by small ligands is often used as a strategy in anti-cancer therapy, alkaloid escholidine seems to be an interesting agent from a medicinal point of view. Berberine, the most known quaternary protoberberine alkaloid (QPA), has been reported to inhibit the SIK3 protein connected with breast cancer. Berberine also appears to reduce the bcl-2 and XIAP expression-proteins responsible for the inhibition of apoptosis. As some problems in the therapy with berberine arose, we studied the DNA binding properties of escholidine, another QPA alkaloid. CD, fluorescence, and NMR examined models of i-motif and G-quadruplex sequences present in the n-myc gene and the c-kit gene. We provide evidence that escholidine does not induce stabilization of the i-motif sequences, while the interaction with G-quadruplex structures appears to be more significant.
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