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Bisintercalation of ditercalinium into a d[CpGpCpG] 2 minihelix: Structure and dynamics aspects—a 400‐MHz 1 H‐nmr study
Author(s) -
Delbarre A.,
Delepierre M.,
D'Estaintot B. Langlois,
Igolen J.,
Roques B. P.
Publication year - 1987
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360260703
Subject(s) - chemistry , dimer , crystallography , helix (gastropod) , stereochemistry , nucleobase , proton nmr , nuclear overhauser effect , two dimensional nuclear magnetic resonance spectroscopy , molecular dynamics , dna , nuclear magnetic resonance spectroscopy , computational chemistry , organic chemistry , ecology , biochemistry , snail , biology
The structure of the complex formed in aqueous solution at pH 5.5 between ditercalinium, a potent antitumoral 7H‐pyrido[4,3‐c]carbazole rigid dimer, and the self‐complementary tetranucleotide d[CpGpCpG], was investigated by 400‐MHz 1 H‐nmr. For a 1:2.5 drug‐to‐helix ratio, the dimer was only found in bound form, whereas free and complexed tetranucleotide were in slow exchange. This allowed unambiguous assignment of the protons in the complex through exchange polarization transfer measurements. The tetranucleotide existed as a right‐handed double helix in the complex. The strong upfield shifts measured on most aromatic protons on both drug and nucleobases as well as on DNA imino protons were consistent with bisintercalation of the dimer. According to the negative nuclear Overhauser effects generated to protons on the convex edge of the bound drug rings by saturation of sugar protons, it was concluded that ditercalinium was intercalated with its rigid bis‐ethyl bispiperidine spacer fitting the major groove of the helix. Difference in antitumor activity of various pyridocarbazole dimers is discussed in relation to the binding kinetics and the complex geometry determined in this study.