Alkaloid Escholidine and Its Interaction with DNA Structures

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F21%3A00123605" target="_blank" >RIV/00216224:14310/21:00123605 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/2079-7737/10/12/1225" target="_blank" >https://www.mdpi.com/2079-7737/10/12/1225</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biology10121225" target="_blank" >10.3390/biology10121225</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Alkaloid Escholidine and Its Interaction with DNA Structures

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Alkaloid Escholidine and Its Interaction with DNA Structures

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

<a href="/cs/project/LM2018127" target="_blank" >LM2018127: Česká infrastruktura pro integrativní strukturní biologii</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

BIOLOGY-BASEL

ISSN

2079-7737

e-ISSN

2079-7737

Svazek periodika

10

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

16

Strana od-do

1-16

Kód UT WoS článku

000736252100001

EID výsledku v databázi Scopus

2-s2.0-85121250096