Binding-induced diversity of a human telomeric G-quadruplex stability phase space

Oblak, Domen (author), Hadži, San (author), Podlipnik, Črtomir (author), Lah, Jurij (author)

The structural polymorphism of G-quadruplex nucleic acids is an important factor in their recognition by proteins and small-molecule ligands. However, it is not clear why the binding of several ligands alters G-quadruplex topology. We addressed this question by following the (un)folding and binding of the human telomeric fragment 5′-(GGGTTA)$_3$GGGT-3′ (22GT) by calorimetry (DSC, ITC) and spectroscopy (CD). A thermodynamic analysis of the obtained data led to a detailed description of the topological phase space of stability (phase diagram) of 22GT and shows how it changes in the presence of a specific bisquinolinium ligand (360A). Various 1:1 and 2:1 ligand–quadruplex complexes were observed. With increasing temperature, the 1:1 complexes transformed into 2:1 complexes, which is attributed to the preferential binding of the ligand to the folding intermediates. Overall, the dissection of the thermodynamic parameters in combination with molecular modelling clarified the driving forces of the topological quadruplex transformations in a wide range of ligand concentrations and temperatures.

• Language: English
• Keywords: G-quadruplex, G-quadruplex stability, G-quadruplex ligand binding, G-quadruplex structure, thermodynamics, DSC, human telomere repeat
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 13 str.
• Numbering: Vol. 15, iss. 9, art. 1150
• PID: 20.500.12556/RUL-154113
• UDC: 577.323
• ISSN on article: 1424-8247
• DOI: 10.3390/ph15091150
• COBISS.SI-ID: 121826051
• Publication date in RUL: 25.01.2024

Record is a part of a journal

• Title: Pharmaceuticals
• Shortened title: Pharmaceuticals
• Publisher: MDPI
• ISSN: 1424-8247
• COBISS.SI-ID: 517582617

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: G-kvadrupleks, stabilnost, vezanje liganda, struktura, termodinamika, DSC

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0201
• Name: Fizikalna kemija

• Funder: ARRS - Slovenian Research Agency
• Project number: J1-1706
• Name: Stabilnost nove vrste kvadruplesov DNA (AGCGA) in njihovo prepoznavanje z nanotelesi