2026-04-17T03:17:42Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1245282025-12-04T19:36:47Zcom_2072_1057col_2072_478813col_2072_478917

00925njm 22002777a 4500 dc Ferreira Aguilera, Rubén author Artali, Roberto author Benoit, Adam author Gargallo Gómez, Raimundo author Eritja i Casadellà, Ramon author Ferguson, David M. author Sham, Yuk Y. author Mazzini, Stefania author 2018-09-13T14:35:39Z 2018-09-13T14:35:39Z 2013-03-15 2018-09-13T14:35:39Z G-quadruplexes are higher-order DNA structures formed from guanine-rich sequences, and have been identified as attractive anticancer drug targets. Elucidating the three-dimensional structure of G-quadruplex with 9-amino acridines and the specific interactions involved in binding selectivity are the key to understanding their mechanism of action. Fluorescence titration assays, competitive dialysis and NMR studies have been used to study the binding specificity of 9-amino acridines to DNA. Structural models of the complexes with the telomeric DNA G-quadruplex based on NMR measurements were developed and further examined by molecular dynamics simulations and free energy calculations. Selective binding of 9-amino acridines for G-quadruplex sequences were observed. These compounds bind between A and G-tetrads, involving significant π-π interactions and several strong hydrogen bonds. The specific interactions between different moieties of the 9-amino acridines to the DNA were examined and shown to play a significant role in governing the overall stabilities of DNA G-quadruplex complexes. Both 9-amino acridines, with similar binding affinities to the G-quadruplex, were shown to induce different level of structural stabilization through intercalation. This unique property of altering structural stability is likely a contributing factor for affecting telomerase function and, subsequently, the observed differences in the anticancer activities between the two 9-amino acridines. ADN Sistemes d'administració de medicaments Telòmer Protons Oligonucleòtids DNA Drug delivery devices Telomere Protons Oligonucleotides Structure and stability of human telomeric G-quadruplex with preclinical 9-amino acridines