TY - JOUR

T1 - Revealing light-induced structural shifts in G-quadruplex-porphyrin complexes: a pulsed dipolar EPR study

AU - Sannikova, Natalya E

AU - Kolokolov, Mikhail I

AU - Khlynova, Tamara A

AU - Chubarov, Alexey S

AU - Polienko, Yuliya F

AU - Fedin, Matvey V

AU - Krumkacheva, Olesya A

N1 - The EPR studies were supported by the Russian Science Foundation (20-73-10239). The calculations were supported by the Ministry of Science and Higher Education (075-15-2021-580). We thank MSHE for granting access to equipment.

PY - 2023/8/23

Y1 - 2023/8/23

N2 - The binding of G-quadruplex structures (G4s) with photosensitizers is of considerable importance in medicinal chemistry and drug discovery due to their promising potential in photodynamic therapy applications. G4s can experience structural changes as a result of ligand interactions and light exposure. Understanding these modifications is essential to uncover the fundamental biological roles of the complexes and optimize their therapeutic potential. The structural diversity of G4s makes it challenging to study their complexes with ligands, necessitating the use of various complementary methods to fully understand these interactions. In this study, we introduce, for the first time, the application of laser-induced dipolar EPR as a method to characterize G-quadruplex DNA complexes containing photosensitizers and to investigate light-induced structural modifications in these systems. To demonstrate the feasibility of this approach, we studied complexes of the human telomeric G-quadruplex (HTel-22) with cationic 5,10,15,20-tetrakis(1-methyl-4-pyridinio) porphyrin tetra(p-toluenesulfonate) (TMPyP4). In addition to showcasing a new methodology, we also aimed to provide insights into the mechanisms underlying photoinduced HTel-22/TMPyP4 structural changes, thereby aiding in the advancement of approaches targeting G4s in photodynamic therapy. EPR revealed G-quadruplex unfolding and dimer formation upon light exposure. Our findings demonstrate the potential of EPR spectroscopy for examining G4 complexes with photosensitizers and contribute to a better understanding of G4s' interactions with ligands under light.

AB - The binding of G-quadruplex structures (G4s) with photosensitizers is of considerable importance in medicinal chemistry and drug discovery due to their promising potential in photodynamic therapy applications. G4s can experience structural changes as a result of ligand interactions and light exposure. Understanding these modifications is essential to uncover the fundamental biological roles of the complexes and optimize their therapeutic potential. The structural diversity of G4s makes it challenging to study their complexes with ligands, necessitating the use of various complementary methods to fully understand these interactions. In this study, we introduce, for the first time, the application of laser-induced dipolar EPR as a method to characterize G-quadruplex DNA complexes containing photosensitizers and to investigate light-induced structural modifications in these systems. To demonstrate the feasibility of this approach, we studied complexes of the human telomeric G-quadruplex (HTel-22) with cationic 5,10,15,20-tetrakis(1-methyl-4-pyridinio) porphyrin tetra(p-toluenesulfonate) (TMPyP4). In addition to showcasing a new methodology, we also aimed to provide insights into the mechanisms underlying photoinduced HTel-22/TMPyP4 structural changes, thereby aiding in the advancement of approaches targeting G4s in photodynamic therapy. EPR revealed G-quadruplex unfolding and dimer formation upon light exposure. Our findings demonstrate the potential of EPR spectroscopy for examining G4 complexes with photosensitizers and contribute to a better understanding of G4s' interactions with ligands under light.

KW - DNA/chemistry

KW - G-Quadruplexes

KW - Humans

KW - Ligands

KW - Photosensitizing Agents

KW - Porphyrins/chemistry

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85168787392&origin=inward&txGid=ffa8ffb90efead63cf5bec1f7decf6fb

UR - https://www.mendeley.com/catalogue/b684ef17-2a71-3b56-ab77-3ea607d360bd/

U2 - 10.1039/d3cp01775c

DO - 10.1039/d3cp01775c

M3 - Article

C2 - 37581249

VL - 25

SP - 22455

EP - 22466

JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

SN - 1463-9076

IS - 33

ER -