Selective interactions of perylene derivatives having different side chains with inter- and intramolecular G-quadruplex DNA structures. A correlation with telomerase inhibition.
While the importance of the aromatic core in small organic molecules, studied as G-quadruplex mediated telomerase inhibitors, appears well studied by a number of researches, the role of side chains has been less well characterized. In this paper, we have studied the ability of six perylene derivatives with different side chains to induce both inter- and intramolecular G-quadruplex structures. The distance between the aromatic core and the positive charges in the side chains emerges as a significant molecular feature in G-quadruplex formation. Furthermore, the G-quadruplex formation appears also related to drugs 'self-association', influenced by the side chains basicity. The different efficiencies of the six perylene derivatives in interacting both with inter- and intramolecular G-quadruplex structures satisfactorily correlate with telomerase inhibition in cell-free systems.
Rossetti
Luigi
L
Dipartimento di Genetica e Biologia Molecolare, Università di Roma La Sapienza Piazzale A. Moro 5, 00185 Roma, Italy.
Franceschin
Marco
M
Schirripa
Stefano
S
Bianco
Armandodoriano
A
Ortaggi
Giancarlo
G
Savino
Maria
M
D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D054856:G-Quadruplexes; D006801:Humans; D010569:Perylene / Q000737:chemistry / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry
D004791:Enzyme Inhibitors; D010569:Perylene; D004247:DNA; D019098:Telomerase