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1 H‐ and 31 P‐nmr studies of ditercalinium binding to a d(GCGC) 2 and d(CCTATAGG) 2 minihelices: A sequence specificity study
Author(s) -
Delepierre Muriel,
Milhe Catherine,
Namane Abdelkader,
Dinh Tam Huynh,
Roques Bernard P.
Publication year - 1991
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.360310307
Subject(s) - chemistry , intercalation (chemistry) , nucleotide , crystallography , proton , oligonucleotide , proton nmr , helix (gastropod) , chemical shift , stereochemistry , nuclear magnetic resonance spectroscopy , dna , intermolecular force , base pair , chromophore , side chain , molecule , inorganic chemistry , photochemistry , organic chemistry , biochemistry , ecology , physics , quantum mechanics , biology , snail , gene , polymer
The structures of the complexes formed in aqueous solution between ditercalinium, a bisintercalating drug, and both the self‐complementary tetranucleotide d(GCGC) 2 and octanucleotided(CCTATAGG) 2 , have been investigated by 400‐MHz 1 H‐nmr and 162‐MHz 31 P‐nmr. All the nonexchangeable protons, as well as the exchangeable imino protons and the phosphorus signals, have been assigned. Both oligonucleotides have been shown to adopt a right‐handed B‐DNA type structure. The addition of ditercalinium to the oligo‐nucleotides lead to the formation of complexes in slow exchange at the nmr time scale with the free helices. At all drug‐to‐helix ratios studied, the ditercalinium was found in the bound form, whereas free and complexed oligonucleotides were in slow exchange, allowing resonance assignments through two‐dimensional chemical exchange experiments. For d(GCGC) 2 the strong upfield shifts induced on all aromatic protons of both the bases and the drug by complexation with ditercalinium suggest an interaction by intercalation of the two rings. However, the loss of twofold symmetry upon binding, as well as the chemical shift variation of the drug proton signals of one of the chromophores with temperature and concentration, favor a model in which the drug–nucleotide complexes have one ring of the drug intercalated and the other stacked on top of the external base pair. The intermolecular contacts between drug protons and nucleotide protons give a defined geometry for complexation that is consistent with the proposed model. In contrast, with d(CCTATAGG) 2 several drug–nucleotide complexes were formed and a large increase in line broadening was observed at high drug‐to‐DNA ratios, precluding a detailed analysis of these complexes. However, the large upfield shift in the imino proton resonances together with the shielding of the ditercalinium ring protons favor a model with bis‐intercalation of ditercalinium. This model is supported by the downfield shift of at least 4 out of 14 phosphorus signals. The results are compared with those obtained on ditercalinium binding to the homologous sequences d(CGCG) 2 and d(TTCGCGAA) 2 , and discussed in terms of sequence specificity.