Structure of the first parallel DNA quadruplex-drug complex.
The first crystal structure of a drug (daunomycin) bound to a parallel-stranded intermolecular telomeric G4 quadruplex (d(TGGGGT)4) has been determined to high resolution. A planar assemblage of three daunomycin molecules stacks onto the 5' end of the G4 column, with the daunosamine substituents occupying three of the four quadruplex grooves. The surface area of the terminal G-quartet in this parallel DNA quadruplex, presently occupied by three daunomycins, is sufficiently large that it could easily accommodate other potential telomerase inhibitors such as substituted porphyrins or telomestatin.
Clark
George R
GR
Department of Chemistry, University of Auckland, Auckland, New Zealand. g.clark@auckland.ac.nz
Pytel
Patrycja D
PD
Squire
Christopher J
CJ
Neidle
Stephen
S
D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D003630:Daunorubicin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D054856:G-Quadruplexes; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
D000903:Antibiotics, Antineoplastic; D004247:DNA; D003630:Daunorubicin