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Seminar by Prof. Liliya A. Yatsunyk, Swarthmore College, USA

Le 30/04/2019
De 16h30 à 18h00
Faculté de chimie, salle verte

Titre:
Interactions between G-quadruplex DNA and porphyrin ligands

Abstract:
Non-canonical DNA structures, notably quadruplexes, are gaining popularity because biological evidence suggests that they play their crucial roles in a variety of disease-related biological processes. G-quadruplex DNA structures are composed of planar guanine tetrads which are engaged in effective p-p stacking and are further stabilized by monovalent central cation (e.g. K+ or Na+), Figure 1A. Sequences with G-quadruplex forming potential are present in telomeres and in oncogene promoters, according to bioinformatics studies.
Here I will discuss our structural and biophysical characterization of a variety of telomeric and oncogene promoter DNA sequences (e.g. human telomeric DNA (Tel22); telomeric DNA from Tetrahymena thermofila (THM); human c-Myc oncogene promoter) in complex with N-methylmesoporphyrin IX (NMM), derivatives of 5,10,15,20-tetra-N-methylpyridyl porphyrin (TMPyP4), and other porphyrins. Due to the excellent optical properties of porphyrins, we investigated their binding to G-quadruplex DNA using UV-vis and fluorescence titrations. We determined stoichiometries for binding events independently via the Job plot method. We obtained thermodynamic parameters via ITC titrations. We crystallized NMM in complex with Tel22 and THM (Figure 1B, C). Our findings are of great importance for the development of new and efficient anticancer