Thompson, A. S., & Hurley, L. H. (1995). Solution conformation of a bizelesin A-tract duplex adduct: DNA-DNA cross-linking of an A-tract straightens out bent DNA. Journal of Molecular Biology, 252(1), 86-101.
PMID: 7666436;Abstract:
The DNA cross-linker bizelesin has been previously shown to form interhelical interstrand cross-links with adenine residues six base-pairs apart (including the modified adenine residues). Sequence specificity studies have shown that the ligand has a high affinity for the intrinsically bent A-tract sequence [d(CGTTTTTACG):d(CGTAAAAACG)]. However, gel retardation studies have shown that the cross-linked duplex retains none of the characteristic A-tract bending observed within the unmodified duplex. Two-dimensional 1H-NMR experiments have not only confirmed the sites of cross-linking into the duplex, but have also shown the loss of inherent A-tract characteristics, including reduced crosspeak intensities between the H2s of the central adenine residues and the cross-strand H1' of the base one base removed to the 3' side. This observation suggests loss of propeller twisting within these central adenine residues and provides insight into the controversial origin of A-tract bending. This study is important because it validates the use of bizelesin as a probe for determining the importance of A-tract-induced bending in transcriptional and replicational elements.
Hansen, M., & Hurley, L. (1995). Altromycin B threads the DNA helix interacting with both the major and the minor grooves to position itself for site-directed alkylation of guanine N7. Journal of the American Chemical Society, 117(9), 2421-2429.
Abstract:
The pluramycins are a class of antitumor antibiotics for which a detailed structural investigation of their interaction with DNA is lacking. Using altromycin B as a prototypical pluramycin, we have characterized the drug's interaction with the self-complementary DNA duplex [d(GAAG*TACTTC)]2 diadduct (*denotes the site of covalent modification) by two-dimensional NMR and have gained considerable insight into the role played by the drug's glycosidic substituents in sequence selectivity. The drug intercalates into the DNA molecule and stacks to the 5' side of the modified guanine, thereby placing a disaccharide into the minor groove and a monosaccharide into the major groove. As a result of these interactions, the epoxide is positioned in the major groove of the DNA to perform electrophilic attack on N7 of guanine.
Hurley, L. H., Zmijewski, M., & Chang, C. (1975). Biosynthesis of anthramycin. Determination of the labeling pattern by the use of radioactive and stable isotope techniques. Journal of the American Chemical Society, 97(15), 4372-4378.
PMID: 1141599;Abstract:
The building blocks for anthramycin, an antitumor antibiotic produced by a strain of Streptomyces refuineus, have been shown to be L-tryptophan, probably via 3-hydroxyanthranilic acid, L-tyrosine which loses two of its aromatic carbons, and L-methionine which contributes two methyl groups. While one of the two methyl groups is transferred intact, the other loses all of its hydrogens and becomes the carbonyl of an amide group. A mechanism involving extradiol cleavage of Dopa is proposed on the basis of double labeling and stable isotope experiments. A general scheme for the biosynthetic origin of the C3-proline moieties of anthramycin, lincomycin A, and sibiromycin and the C2-proline moieties of tomaymycin and lincomycin B is proposed.
Thurston, D. E., Kaumaya, P. T., & Hurley, L. H. (1984). Limitations and factors affecting the lactam reduction approach to the synthesis of anthramycin analogs. Tetrahedron Letters, 25(25), 2649-2652.
Abstract:
The limitations and factors affecting the hydride reduction of pyrrolo [1,4]benzodiazepine-5,10-diones to anthramycin-type analogs have been explored. © 1984.
Ostrander, J. M., & Hurley, L. H. (1979). Pyrrolo(1,4)benzodiazepine antibiotics. Biosynthetic conversion of (D) and (L) tyrosine, (15N, 3- and 5-2H2 1-14C)tyrosine and L-(5-3H, indole-15N)tryptophan into anthramycin and sibiromycin. Journal of Natural Products, 42(6), 693-.
