Alkaloid Escholidine and Its Interaction with DNA Structures

J 2021

Alkaloid Escholidine and Its Interaction with DNA Structures

JAROŠOVÁ, Petra, Pavel HANNIG, Kateřina KOLKOVÁ, Stefania MAZZINI, Eva TÁBORSKÁ et. al.

Basic information

Original name

Alkaloid Escholidine and Its Interaction with DNA Structures

Authors

JAROŠOVÁ, Petra (203 Czech Republic, belonging to the institution), Pavel HANNIG (203 Czech Republic, belonging to the institution), Kateřina KOLKOVÁ (203 Czech Republic, belonging to the institution), Stefania MAZZINI, Eva TÁBORSKÁ (203 Czech Republic, belonging to the institution), Raimundo GARGALLO, Gigliola BORGONOVO, Roberto ARTALI and Petr TÁBORSKÝ (203 Czech Republic, guarantor, belonging to the institution)

Edition

BIOLOGY-BASEL, BASEL, MDPI, 2021, 2079-7737

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10406 Analytical chemistry

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.168

RIV identification code

RIV/00216224:14310/21:00123605

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.3390/biology10121225

UT WoS

000736252100001

Keywords in English

escholidine; G-quadruplex; DNA; cancer; alkaloid; spectroscopy

Abstract

V originále

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.

Links

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1192/2020, interní kód MU

Name: Vývoj metod a instrumentace pro analýzu biologicky významných látek 2021

Investor: Masaryk University

Citovat

JAROŠOVÁ, Petra, Pavel HANNIG, Kateřina KOLKOVÁ, Stefania MAZZINI, Eva TÁBORSKÁ, Raimundo GARGALLO, Gigliola BORGONOVO, Roberto ARTALI and Petr TÁBORSKÝ. Alkaloid Escholidine and Its Interaction with DNA Structures. BIOLOGY-BASEL. BASEL: MDPI, 2021, vol. 10, No 12, p. 1-16. ISSN 2079-7737. Available from: https://dx.doi.org/10.3390/biology10121225.

@article{1818527,
   author = {Jarošová, Petra and Hannig, Pavel and Kolková, Kateřina and Mazzini, Stefania and Táborská, Eva and Gargallo, Raimundo and Borgonovo, Gigliola and Artali, Roberto and Táborský, Petr},
   article_location = {BASEL},
   article_number = {12},
   doi = {http://dx.doi.org/10.3390/biology10121225},
   keywords = {escholidine; G-quadruplex; DNA; cancer; alkaloid; spectroscopy},
   language = {eng},
   issn = {2079-7737},
   journal = {BIOLOGY-BASEL},
   title = {Alkaloid Escholidine and Its Interaction with DNA Structures},
   url = {https://www.mdpi.com/2079-7737/10/12/1225},
   volume = {10},
   year = {2021}
}

TY  - JOUR
ID  - 1818527
AU  - Jarošová, Petra - Hannig, Pavel - Kolková, Kateřina - Mazzini, Stefania - Táborská, Eva - Gargallo, Raimundo - Borgonovo, Gigliola - Artali, Roberto - Táborský, Petr
PY  - 2021
TI  - Alkaloid Escholidine and Its Interaction with DNA Structures
JF  - BIOLOGY-BASEL
VL  - 10
IS  - 12
SP  - 1-16
EP  - 1-16
PB  - MDPI
SN  - 20797737
KW  - escholidine
KW  - G-quadruplex
KW  - DNA
KW  - cancer
KW  - alkaloid
KW  - spectroscopy
UR  - https://www.mdpi.com/2079-7737/10/12/1225
N2  - 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.
ER  -

JAROŠOVÁ, Petra, Pavel HANNIG, Kateřina KOLKOVÁ, Stefania MAZZINI, Eva TÁBORSKÁ, Raimundo GARGALLO, Gigliola BORGONOVO, Roberto ARTALI and Petr TÁBORSKÝ. Alkaloid Escholidine and Its Interaction with DNA Structures. \textit{BIOLOGY-BASEL}. BASEL: MDPI, 2021, vol.~10, No~12, p.~1-16. ISSN~2079-7737. Available from: https://dx.doi.org/10.3390/biology10121225.

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