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

RIGO, Riccardo, Elisabetta GROAZ and Claudia SISSI. Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications. PHARMACEUTICALS. BASEL, SWITZERLAND: MDPI, 2022, vol. 15, No 3, p. 373-385. ISSN 1424-8247. Available from: https://dx.doi.org/10.3390/ph15030373.

Basic information

• Original name: Polymorphic and Higher-Order G-Quadruplexes as Possible Transcription Regulators: Novel Perspectives for Future Anticancer Therapeutic Applications
• Authors: RIGO, Riccardo (380 Italy, guarantor, belonging to the institution), Elisabetta GROAZ and Claudia SISSI.
• Edition: PHARMACEUTICALS, BASEL, SWITZERLAND, MDPI, 2022, 1424-8247.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30104 Pharmacology and pharmacy
• Country of publisher: Switzerland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 4.600
• RIV identification code: RIV/00216224:14740/22:00127513
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.3390/ph15030373
• UT WoS: 000774500300001
• Keywords in English: G-quadruplex; folding landscapes; gene promoters
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

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.

Links

• EF20_079/0017045, research and development project: Name: MSCAfellow4@MUNI