Polymorphic and Higher-Order G-Quadruplexes as Possible
Transcription Regulators: Novel Perspectives for Future
Anticancer Therapeutic Applications

J 2022

Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications

RIGO, Riccardo, Elisabetta GROAZ a Claudia SISSI

Základní údaje

Originální název

Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications

Autoři

RIGO, Riccardo (380 Itálie, garant, domácí), Elisabetta GROAZ a Claudia SISSI

Vydání

PHARMACEUTICALS, BASEL, SWITZERLAND, MDPI, 2022, 1424-8247

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.600

Kód RIV

RIV/00216224:14740/22:00127513

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.3390/ph15030373

UT WoS

000774500300001

Klíčová slova anglicky

G-quadruplex; folding landscapes; gene promoters

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 3. 4. 2023 10:12, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

In the past two decades, significant efforts have been put into designing small molecules to target selected genomic sites where DNA conformational rearrangements control gene expression. G-rich sequences at oncogene promoters are considered good points of intervention since, under specific environmental conditions, they can fold into non-canonical tetrahelical structures known as G-quadruplexes. However, emerging evidence points to a frequent lack of correlation between small molecule targeting of G-quadruplexes at gene promoters and the expression of the associated protein, which hampers pharmaceutical applications. The wide genomic localization of G-quadruplexes along with their highly polymorphic behavior may account for this scenario, suggesting the need for more focused drug design strategies. Here, we will summarize the G4 structural features that can be considered to fulfill this goal. In particular, by comparing a telomeric sequence with the well-characterized G-rich domain of the KIT promoter, we will address how multiple secondary structures might cooperate to control genome architecture at a higher level. If this holds true, the link between drug–DNA complex formation and the associated cellular effects will need to be revisited.

Návaznosti

EF20_079/0017045, projekt VaV

Název: MSCAfellow4@MUNI

Citovat

RIGO, Riccardo, Elisabetta GROAZ a Claudia SISSI. Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications. PHARMACEUTICALS. BASEL, SWITZERLAND: MDPI, 2022, roč. 15, č. 3, s. 373-385. ISSN 1424-8247. Dostupné z: https://dx.doi.org/10.3390/ph15030373.

@article{2240876,
   author = {Rigo, Riccardo and Groaz, Elisabetta and Sissi, Claudia},
   article_location = {BASEL, SWITZERLAND},
   article_number = {3},
   doi = {http://dx.doi.org/10.3390/ph15030373},
   keywords = {G-quadruplex; folding landscapes; gene promoters},
   language = {eng},
   issn = {1424-8247},
   journal = {PHARMACEUTICALS},
   title = {Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications},
   url = {https://www.mdpi.com/1424-8247/15/3/373},
   volume = {15},
   year = {2022}
}

TY  - JOUR
ID  - 2240876
AU  - Rigo, Riccardo - Groaz, Elisabetta - Sissi, Claudia
PY  - 2022
TI  - Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications
JF  - PHARMACEUTICALS
VL  - 15
IS  - 3
SP  - 373
EP  - 373
PB  - MDPI
SN  - 14248247
KW  - G-quadruplex
KW  - folding landscapes
KW  - gene promoters
UR  - https://www.mdpi.com/1424-8247/15/3/373
N2  - In the past two decades, significant efforts have been put into designing small molecules to target selected genomic sites where DNA conformational rearrangements control gene expression. G-rich sequences at oncogene promoters are considered good points of intervention since, under specific environmental conditions, they can fold into non-canonical tetrahelical structures known as G-quadruplexes. However, emerging evidence points to a frequent lack of correlation between small molecule targeting of G-quadruplexes at gene promoters and the expression of the associated protein, which hampers pharmaceutical applications. The wide genomic localization of G-quadruplexes along with their highly polymorphic behavior may account for this scenario, suggesting the need for more focused drug design strategies. Here, we will summarize the G4 structural features that can be considered to fulfill this goal. In particular, by comparing a telomeric sequence with the well-characterized G-rich domain of the KIT promoter, we will address how multiple secondary structures might cooperate to control genome architecture at a higher level. If this holds true, the link between drug–DNA complex formation and the associated cellular effects will need to be revisited.
ER  -

RIGO, Riccardo, Elisabetta GROAZ a Claudia SISSI. Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications. \textit{PHARMACEUTICALS}. BASEL, SWITZERLAND: MDPI, 2022, roč.~15, č.~3, s.~373-385. ISSN~1424-8247. Dostupné z: https://dx.doi.org/10.3390/ph15030373.

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