Structural analysis of d(GCAATTGC) sub 2 and its complex with berenil by nuclear magnetic resonance spectroscopy

The structures of d(GCAATTGC){sub 2} and its complex with berenil in solution were analyzed by two-dimensional {sup 1}H NMR spectroscopy. Intra- and internucleotide nuclear Overhauser effect (NOE) connectivities demonstrate that the octanucleotide duplex is primarily in the B conformation. Binding w...

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Bibliographic Details
Published inBiochemistry (Easton) Vol. 29:28
Main Authors Yoshida, Mitsuru, Banville, D.L., Shafer, R.H.
Format Journal Article
LanguageEnglish
Published United States 17.07.1990
Subjects
550201 - Biochemistry- Tracer Techniques
ADENINES
AMIDINES
AMINES
ANTIMETABOLITES
AROMATICS
AZAARENES
BARYONS
BASIC BIOLOGICAL SCIENCES
CHEMICAL SHIFT
DNA
DRUGS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HETEROCYCLIC COMPOUNDS
MAGNETIC RESONANCE
MATHEMATICAL MODELS
MOLECULAR MODELS
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACID DENATURATION
NUCLEIC ACIDS
NUCLEONS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OVERHAUSER EFFECT
PROTONS
PURINES
RESONANCE
TRYPANOSOMES
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Summary:The structures of d(GCAATTGC){sub 2} and its complex with berenil in solution were analyzed by two-dimensional {sup 1}H NMR spectroscopy. Intra- and internucleotide nuclear Overhauser effect (NOE) connectivities demonstrate that the octanucleotide duplex is primarily in the B conformation. Binding with berenil stabilizes the duplex with respect to thermal denaturation by about 10{degree}C, based on the appearance of the imino proton signals. The berenil-d(GCAATTGC){sub 2} system is in fast exchange on the NMR time scale. The two-dimensional NMR data reveal that berenil binds in the minor groove of d(GCAATTGC){sub 2}. The aromatic drug protons are placed within 5 {angstrom} of the H2 proton of both adenines, the H1{prime}, H5{prime}, and H5{double prime} of both thymidines, and the H4{prime}, H5{prime}, and H5{double prime} of the internal guanosine. The amidine protons on berenil are also close to the H2 proton of both adenines. The duplex retains an overall B conformation in the complex with berenil. At 18{degree}C, NOE contacts at longer mixing times indicate the presence of end-to-end association both in the duplex alone and also in its complex with berenil. These intermolecular contacts either vanished or diminished substantially at 45{degree}C. Two molecular models are proposed for the berenil-(GCAATTGC){sub 2} complex; one has hydrogen bonds between the berenil amidine protons and the carbonyl oxygen, O2, of the external thymines, and the other has hydrogen bonds between the drug amidine protons and the purine nitrogen, N3, of the internal adenines. Quantitative analysis of the NOE data favors the second model.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00480a006