title: Structural and conformational requisites in DNA quadruplex groove binding: another piece to the puzzle.
abstract: The study of DNA G-quadruplex stabilizers has enjoyed a great momentum in the late years due to their application as anticancer agents. The recognition of the grooves of these structural motifs is expected to result in a higher degree of selectivity over other DNA structures. Therefore, to achieve an enhanced knowledge on the structural and conformational requisites for quadruplex groove recognition, distamycin A, the only compound for which a pure groove binding has been proven, has been chemically modified. Surprisingly, structural and thermodynamic studies revealed that the absence of Coulombic interactions results in an unprecedented binding position in which both the groove and the 3' end of the DNA are occupied. This further contribution adds another piece to the so far elusive puzzle of the recognition between ligands and DNA quadruplexes and will serve as a platform for a rational design of new groove binders.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, via D. Montesano 49, I-80131 Napoli, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Trotta
authors.forename: Ada
authors.initials: A
authors.lastname: Virno
authors.forename: Stefano
authors.initials: S
authors.lastname: De Tito
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Bruno
authors.initials: B
authors.lastname: Pagano
authors.forename: Vittorio
authors.initials: V
authors.lastname: Limongelli
authors.forename: Concetta
authors.initials: C
authors.lastname: Giancola
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Luciano
authors.initials: L
authors.lastname: Mayol
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Antonio
authors.initials: A
authors.lastname: Randazzo
mesh_terms: D001483:Base Sequence; D001966:Bromine / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004214:Distamycins / Q000737:chemistry / Q000378:metabolism; D054856:G-Quadruplexes; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D004214:Distamycins; D009838:Oligodeoxyribonucleotides; C030000:stallimycin; D004247:DNA; D001966:Bromine