Structural and Conformational Requisites in DNA Quadruplex Groove Binding: Another Piece to the Puzzle

• Published in: Journal of the American Chemical Society 2010-05, Vol.132 (18), p.6425-6433
• Main Authors: Cosconati, Sandro, Marinelli, Luciana, Trotta, Roberta, Virno, Ada, De Tito, Stefano, Romagnoli, Romeo, Pagano, Bruno, Limongelli, Vittorio, Giancola, Concetta, Baraldi, Pier Giovanni, Mayol, Luciano, Novellino, Ettore, Randazzo, Antonio
• Format: Article
• Language: English
• Subjects: Base Sequence; Bromine - chemistry; Distamycins - chemistry; Distamycins - metabolism; DNA - chemistry; DNA - genetics; DNA - metabolism; G-Quadruplexes; Magnetic Resonance Spectroscopy; Models, Molecular; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - genetics; Oligodeoxyribonucleotides - metabolism; Thermodynamics
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja1003872

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.