NMR characterization of a heterocomplex formed by distamycin and its analog 2-ImD with d(CGCAAGTTGGC):d(GCCAACTTGCG). Preference for the 1:1:1 2-ImD:Dst:DNA complex over the 2:1 2-ImD:DNA and the 2:1 Dst:DNA complexes

Journal Article · Wed Jun 02 00:00:00 EDT 1993 · Journal of the American Chemical Society; (United States)

DOI:https://doi.org/10.1021/ja00064a009· OSTI ID:6235201

Geierstanger, B H; Dwyer, T J; Wemmer, D E ^[1]; Bathini, Y; Lown, J W ^[2]

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1. Univ. of California, Berkeley (United States)
2. Univ. of Alberta, Edmonton (Canada)

The minor-groove binder distamycin (Dst), its pyrrole-imidazole-pyrrole analog, 2-imidazole-distamycin (2-ImD), and the oligonucleotide d(CGCAAGTTGGC):d(GCCAACTTGCG) were found to form a 1:1:1 2-ImD-Dst:DNA complex. As characterized by 2D NOE spectroscopy combined with molecular modeling, one 2-ImD and one Dst molecule bind simultaneously in a head-to-tail orientation contacting the minor groove of the central AAGTT:AACTT site. The 2-ImD ligand lies along the AAGTT strand with the imidazole nitrogen of the ligand specifically interacting with the guanine amino group. The distamycin ligand lies along the AACTT strand. The molecular structure of the 1:1:1 2-ImD:Dst:DNA complex is very similar to those of the complexes formed between two 2-ImD molecules (2:1 2-ImD:DNA complex) or two distamycin molecules (2:1 Dst:DNA complex) and the same oligonucleotide duplex. Competition titrations confirm that the 1:1:1 2-ImD:Dst:DNA complex forms preferentially over the 2:1 2-ImD:DNA complex, as well as over the newly discovered 2:1 Dst:DNA complex. These results indicate that (i) the hydrogen-bond-accepting imidazole nitrogen of the 2-ImD ligand in the 1:1:1 2-ImD:Dst:DNA complex is responsible for the strand-specific recognition of a GC base pair, (ii) the availability of a single hydrogen bond acceptor on the ligand molecule per guanine amino group enhanced both specificity and affinity of DNA binding, and (iii) different distamycin-like ligands can be combined in the 2:1 binding motif to expand the range of DNA sequences that can be specifically recognized through the minor groove. 18 refs., 7 figs., 4 tabs.

• DOE Contract Number: FG05-86ER75281
• OSTI ID: 6235201
• Journal Information: Journal of the American Chemical Society; (United States), Vol. 115:11; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
COMPLEXES
SPECTROSCOPY
EXPERIMENTAL DATA
HEAVY WATER
HETEROCYCLIC COMPOUNDS
LIGANDS
NUCLEAR MAGNETIC RESONANCE
OLIGONUCLEOTIDES
TITRATION
DATA
HYDROGEN COMPOUNDS
INFORMATION
MAGNETIC RESONANCE
NUCLEIC ACIDS
NUMERICAL DATA
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
RESONANCE
WATER
400201* - Chemical & Physicochemical Properties
400102 - Chemical & Spectral Procedures