title: The triazatruxene derivative azatrux binds to the parallel form of the human telomeric G-quadruplex under molecular crowding conditions: biophysical and molecular modeling studies.
abstract: The present study has employed a combination of spectroscopic, calorimetric and computational methods to explore the binding of the three side-chained triazatruxene derivative, termed azatrux, to a human telomeric G-quadruplex sequence, under conditions of molecular crowding. The binding of azatrux to the tetramolecular parallel [d(TGGGGT)](4) quadruplex in the presence and absence of crowding conditions, was also characterized. The data indicate that azatrux binds in an end-stacking mode to the parallel G-quadruplex scaffold and highlights the key structural elements involved in the binding. The selectivity of azatrux for the human telomeric G-quadruplex relative to another biologically relevant G-quadruplex (c-Kit87up) and to duplex DNA was also investigated under molecular crowding conditions, showing that azatrux has good selectivity for the human telomeric G-quadruplex over the other investigated DNA structures.
authors.affiliation: Dipartimento di Chimica P. Corradini, Università di Napoli Federico II, via Cintia 4, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Petraccone
authors.forename: Iolanda
authors.initials: I
authors.lastname: Fotticchia
authors.forename: Annunziata
authors.initials: A
authors.lastname: Cummaro
authors.forename: Bruno
authors.initials: B
authors.lastname: Pagano
authors.forename: Luca
authors.initials: L
authors.lastname: Ginnari-Satriani
authors.forename: Shozeb
authors.initials: S
authors.lastname: Haider
authors.forename: Antonio
authors.initials: A
authors.lastname: Randazzo
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
authors.forename: Concetta
authors.initials: C
authors.lastname: Giancola
mesh_terms: D001703:Biophysics; D002151:Calorimetry / Q000379:methods; D002227:Carbazoles / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D016615:Telomere / Q000235:genetics / Q000378:metabolism
chemical_list: D002227:Carbazoles; D010880:Piperidines; C568450:azatrux; D004247:DNA