Kwok, Y., Sun, D., Clement, J. J., & Hurley, L. H. (1999). The quinobenzoxazines: Relationship between DNA binding and biological activity. Anti-Cancer Drug Design, 14(5), 443-450.
PMID: 10766299;Abstract:
The quinobenzoxazine compounds, derived from antibacterial quinolones, is active in vitro and in vivo against murine and human tumors. In this contribution, we show that the relative DNA binding affinity of the quinobenzoxazine compounds correlates with their cytotoxicity, their ability to inhibit gyrase-DNA complex formation, and the decatenation of kinetoplast DNA by human topoisomerase II. DNA binding studies with the descarboxy-A-62176 analogue indicate that the β-keto acid moiety of the quinobenzoxazine compounds plays an important role in their interaction with DNA.
Hurley, L. H. (1979). Pyrrolo[1,4]benzodiazepine antibiotics. Biosynthetic conversion of tyrosine to the C2- and C3-proline moieties of anthramycin, tomaymycin, and sibiromycin. Biochemistry, 18(19), 4230-4237.
PMID: 582801;Abstract:
This paper describes biosynthetic labeling experiments on the conversion of tyrosine to the C2- and C3-proline units of anthramycin, tomaymycin, and sibiromycin. The biosynthetic fate of all of the aromatic and side-chain hydrogens has been determined in each antibiotic by using dual tagged (3H/14C) and 2H-labeled tyrosine molecules. In addition, experiments using [15N]tyrosine and the tritiated D and L isomers of tyrosine have shed some light on the biochemical reactions which take place at the α position of tyrosine. On the basis of results of all these experiments, a biosynthetic scheme has been proposed to rationalize the apparent inconsistencies which occur between the results for the three antibiotics. This scheme proposes that a common main pathway involving proximal extradiol cleavage of Dopa and condensation to form the pyrrolo ring leads ultimately to a C-7 branch point compound. Parallel pathways from this central branch point compound lead by well-known biochemical transformations to the C2- and C3-proline units of anthramycin, tomaymycin, and sibiromycin. The reactions in these parallel pathways are suggested to be "cosmetic or after events". © 1979 American Chemical Society.
Cashman, D. J., Buscaglia, R., Freyer, M. W., Dettler, J., Hurley, L. H., & Lewis, E. A. (2008). Molecular modeling and biophysical analysis of the c-MYC NHE-III1 silencer element. Journal of Molecular Modeling, 14(2), 93-101.
PMID: 18087730;Abstract:
G-Quadruplex and i-Motif-forming sequences in the promoter regions of several oncogenes show promise as targets for the regulation of oncogenes. In this study, molecular models were created for the c-MYC NHE-III1 (nuclease hypersensitivity element III1) from two 39-base complementary sequences. The NHE modeled here consists of single folded conformers of the polypurine intramolecular G-Quadruplex and the polypyrimidine intramolecular i-Motif structures, flanked by short duplex DNA sequences. The G-Quadruplex was based on published NMR structural data for the c-MYC 1:2:1 loop isomer. The i-Motif structure is theoretical (with five cytosine-cytosine pairs), where the central intercalated cytosine core interactions are based on NMR structural data obtained for a tetramolecular [d(A2 C4)4] model i-Motif. The loop structures are in silico predictions of the c-MYC i-motif loops. The porphyrin meso-tetra(N-methyl-4-pyridyl)porphine (TMPyP4), as well as the ortho and meta analogs TMPyP2 and TMPyP3, were docked to six different locations in the complete c-MYC NHE. Comparisons are made for drug binding to the NHE and the isolated G-Quadruplex and i-Motif structures. NHE models both with and without bound cationic porphyrin were simulated for 100 ps using molecular dynamics techniques, and the non-bonded interaction energies between the DNA and porphyrins calculated for all of the docking interactions. © Springer-Verlag 2007.
Cathers, B. E., Sun, D., & Hurley, L. H. (1999). Accurate determination of quadruplex binding affinity and potency of G-quadruplex-interactive telomerase inhibitors by use of a telomerase extension assay requires varying the primer concentration. Anti-Cancer Drug Design, 14(4), 367-372.
Kshirsagar, T. A., & Hurley, L. H. (1998). A facile synthesis of 5-mesyl-3-benzylbenz[e]indole: Implications for the involvement of a p-quinone methide intermediate. Journal of Organic Chemistry, 63(16), 5722-5724.
