Synthesis of distamycin A polyamides targeting G-quadruplex DNA.
A number of amide-linked oligopyrroles based on distamycin molecules have been synthesized by solid-state methods, and their interactions with a human intramolecular G-quadruplex have been measured by a melting procedure. Several of these molecules show an enhanced ratio of quadruplex vs. duplex DNA binding compared to distamycin itself, including one with a 2,5-disubstituted pyrrole group. Quadruplex affinity increases with the number of pyrrole groups, and it is suggested that this is consistent with a mixed groove/G-quartet stacking binding mode.
Moore
Michael J B
MJ
Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London, UK WC1N 1AX.
Cuenca
Francisco
F
Searcey
Mark
M
Neidle
Stephen
S
D004247:DNA / Q000737:chemistry*; D019281:Dimerization; D004214:Distamycins / Q000138:chemical synthesis* / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D009757:Nylons / Q000138:chemical synthesis* / Q000737:chemistry; D013816:Thermodynamics
D004214:Distamycins; D009757:Nylons; C030000:stallimycin; D004247:DNA