1. Porphyrin Binding and Irradiation Promote G-Quadruplex DNA Dimeric Structure
- Author
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Aurelien Thureau, M. Longo, Anne Martel, Alessandro Paciaroni, Caterina Petrillo, Valeria Libera, Giorgio Schirò, Lucia Comez, Elena A. Andreeva, Dipartimento di Fisica e Geologia [Perugia], Università degli Studi di Perugia (UNIPG), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), European Synchrotron Radiation Facility (ESRF), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Jülich Centre for Neutron Science (JCNS), Forschungszentrum Jülich GmbH at Heinz Maier-Leibnitz Zentrum (MLZ), and Università degli Studi di Perugia = University of Perugia (UNIPG)
- Subjects
Porphyrins ,Dimer ,MESH: Molecular Structure ,010402 general chemistry ,G-quadruplex ,SEQUENCE ,01 natural sciences ,MESH: Circular Dichroism ,Scattering ,03 medical and health sciences ,chemistry.chemical_compound ,MESH: X-Rays ,ABSORPTION ,Scattering, Radiation ,General Materials Science ,Physical and Theoretical Chemistry ,MESH: Scattering, Radiation ,Protein secondary structure ,030304 developmental biology ,0303 health sciences ,MESH: Porphyrins ,Radiation ,Molecular Structure ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Circular Dichroism ,X-Rays ,MESH: DNA ,CATIONIC PORPHYRINS ,DNA ,Telomere ,Porphyrin ,Small molecule ,0104 chemical sciences ,G-Quadruplexes ,chemistry ,MESH: Dimerization ,Nucleic acid ,Biophysics ,Protein quaternary structure ,LIGAND ,MESH: Telomere ,TELOMERE G-QUADRUPLEX ,Dimerization ,TMPYP4 ,MESH: G-Quadruplexes - Abstract
International audience; Nucleic acid sequences rich in guanines can organize into noncanonical DNA G-quadruplexes (G4s) of variable size. The design of small molecules stabilizing the structure of G4s is a rapidly growing area for the development of novel anticancer therapeutic strategies and bottom-up nanotechnologies. Among a multitude of binders, porphyrins are very attractive due to their light activation that can make them valuable conformational regulators of G4s. Here, a structure-based strategy, integrating complementary probes, is employed to study the interaction between TMPyP4 porphyrin and a 22-base human telomeric sequence (Tel22) before and after irradiation with blue light. Porphyrin binding is discovered to promote Tel22 dimerization, while light irradiation of the Tel22-TMPyP4 complex controls dimer fraction. Such a change in quaternary structure is found to be strictly correlated with modifications at the secondary structure level, thus providing an unprecedented link between the degree of dimerization and the underlying conformational changes in G4s.
- Published
- 2021
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