The molecular structure of triostin A, a cyclic octadepsipeptide antibiotic, has been solved complexed to a DNA double helical fragment with the sequence CGTACG (C, cytosine; G, guanine; T, thymine; A, adenine). The two planar quinoxaline rings of triostin A bis intercalate on the minor groove of the DNA double helix surrounding the CG base pairs at either end. The alanine residues form hydrogen bonds to the guanines. Base stacking in the DNA is perturbed, and the major binding interaction involves a large number of van der Waals contacts between the peptides and the nucleic acid. The adenine residues in the center are in the syn conformation and are paired to thymine through Hoogsteen base pairing.

The structure of a DNA octamer d(GCGTACGC) cocrystallized with the bisintercalator antibiotic triostin A has been solved. The DNA forms an unwound right-handed double helix. Four base pairs are of the Watson-Crick type while four are Hoogsteen base pairs, including two A.T and two G.C base pairs. This is the first observation in an oligonucleotide of Hoogsteen G.C base pairs where the cystosine is protonated. It is likely that these also occur in solutions of DNA complexed to this antibiotic.

The crystal structure of d(CCCCGGGG) has been determined at a resolution of 2.25 A. The oligomers crystallize as A-DNA duplexes occupying crystallographic two-fold axes. The backbone conformation is, in general, similar to that observed in previously reported crystal structures of A-DNA fragments, except for the central linkage, where it adopts an extended structure resulting from all trans conformation at the P-O5'-C5'-C4' bonds. This type of conformation facilitates interstrand stacking between the guanines at the C-G site. The local helix twist at this step is very small (25 degrees) compared to an overall average of 33.5 degrees. The unique structure of the C-G base-pair step, namely the extended backbone and the distinct stacking geometry, may be an important feature in the recognition mechanism between double-stranded DNA molecules and restriction endonucleases such as Msp I, which cuts the sequence CCGG very specifically with a rate unaffected by neighboring base pairs.

Nuclear magnetic resonance spectra (proton and phosphorus-31) and ultraviolet absorption spectra of the DNA decamer d(br5CGbr5CGATbr5CGbr5CG), in which the central two adenine-thymine base pairs are out of order with the rest of the purine-pyrimidine alternation sequence, indicate that under appropriate solvent conditions (high salt and methanol) the molecule undergoes a structural transition from a right-handed B-DNA conformation to a left-handed Z-DNA conformation. Measurements of the two-dimensional nuclear Overhauser effect on the decamer indicate that all of the guanines as well as the two equivalent thymines adopt the syn conformation.

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