The number and distances of positive charges of polyamine side chains in a series of perylene diimides significantly influence their ability to induce G-quadruplex structures and inhibit human telomerase.
We have synthesized eight polyamine perylene diimides to conjugate the efficiency of perylene derivatives in stabilizing G-quadruplex structures and the polyamines' biological activity, due to specific interactions with different DNA domains. Our study was carried out by investigating the ability of these derivatives to induce inter- and intramolecular G-quadruplex structures by polyacrylamide gel electrophoresis (PAGE) and to inhibit telomerase in a modified TRAP assay. The two properties appear to be satisfactorily correlated and they show that the number and distances of positive charges in the side chains dramatically influence both these features. Although our previous studies on perylene derivatives with mono-positively charged side chains indicated that self assembly in aqueous solution leads to a major efficiency, the result observed with the spermine derivative suggests that a too strong aggregation is unfavourable, because it determines a lower solubility of the compounds.
Franceschin
Marco
M
Dipartimento di Chimica, Università di Roma "La Sapienza", Piazzale A. Moro 5, 00185 Roma, Italy.
Lombardo
Caterina Maria
CM
Pascucci
Emanuela
E
D'Ambrosio
Danilo
D
Micheli
Emanuela
E
Bianco
Armandodoriano
A
Ortaggi
Giancarlo
G
Savino
Maria
M
D002412:Cations / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D006860:Hydrogen Bonding; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D010569:Perylene / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D013053:Spectrophotometry; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
D002412:Cations; D004791:Enzyme Inhibitors; D007094:Imides; D011073:Polyamines; D010569:Perylene; D004247:DNA; D019098:Telomerase