Mehta, A. K., Shayo, Y., Vankayalapati, H., Hurley, L. H., & Schaefer, J. (2004). Structure of a quinobenzoxazine-G-quadruplex complex by REDOR NMR. Biochemistry, 43(38), 11953-11958.
PMID: 15379535;Abstract:
Rotational-echo double resonance solid-state 31P{19F} and 13C{19F} NMR spectra have been used to locate the binding of a fluoroquinobenzoxazine to a DNA G-quadruplex labeled by phosphorothioation and [methyl-13C]thymidine.
Sun, D., & Hurley, L. H. (2001). Targeting telomeres and telomerase. Methods in Enzymology, 340, 573-592.
Hannan, M. A., Hurley, L. H., & Gairola, C. (1978). Mutagenic and recombinogenic effects of the antitumor antibiotic anthramycin. Cancer Research, 38(9), 2795-2799.
PMID: 354779;Abstract:
Anthramycin, one of the pyrrolo(1,4)benzodiazepine antibiotics with potent antitumor activity, was tested for its effects on a number of genetic parameters. The results show that this antibiotic is nonmutagenic in the Ames strains of Salmonella typhimurium while mutagenic in only one and antimutagenic in the rest of the genes tested in the eukaryotic organism Saccharomyces cerevisiae. The antibiotic is, however, a potent recombinogen in as much as it reduced mitotic crossing over, mitotic gene conversion, and possibly other chromosomal alterations in a diploid strain of S. cerevisiae. These studies emphasize the need for a battery of test systems including eukaryotic organisms to detect the genetic activity of certain antitumor drugs. The importance of considering data distinguishing between highly mutagenic and poorly mutagenic cancer chemotherapeutic agents is also discussed.
Thurston, D. E., Bose, D. S., Thompson, A. S., Howard, P. W., Leoni, A., Croker, S. J., Jenkins, T. C., Neidle, S., Hartley, J. A., & Hurley, L. H. (1996). Synthesis of sequence-selective C8-linked pyrrolo[2,1-c][1,4]benzodiazepine DNA interstrand cross-linking agents. Journal of Organic Chemistry, 61(23), 8141-8147.
Abstract:
An efficient convergent synthesis of a homologous series of C8-linked pyrrolobenzodiazepine dimers with remarkable DNA interstrand cross-linking activity and potent in vitro cytotoxicity is reported. The 'amino thioacetal' cyclization procedure was used to produce the electrophilic DNA-interactive N10-C11 imine moiety during the final synthetic step. In order to construct the key A-ring fragments (9a-d), a versatile convergent approach has been developed to join two units of vanillic acid with α,ω-dihaloalkanes of varying length to provide the required bis(4-carboxy-2-methoxyphenoxy)alkanes while avoiding the formation of mixtures of monoalkylated and bisalkylated products.
Sun, D., Lin, C. H., & Hurley, L. H. (1993). A-tract and (+)-CC-1065-induced bending of DNA. Comparison of structural features using non-denaturing gel analysis, hydroxyl-radical footprinting, and high-field NMR. Biochemistry, 32(17), 4487-4495.
PMID: 8387334;Abstract:
(+)-CC-1065 is a biologically potent DNA-reactive antitumor antibiotic produced by Streptomyces zelensis. In a previous study we have reported that (+)-CC-1065 produces bending of DNA that has similarities to that intrinsically associated with A-tracts [Lin, C. H., Sun, D., & Hurley, L. H. (1991) Chem. Res. Toxicol. 4, 21-26]. In this article we provide evidence using a combination of non-denaturing gel analysis, hydroxyl-radical footprinting, and high-field NMR for both distinctions between the two types of bends and the importance of junctions in both types of bends. For A-tracts we demonstrate that the locus of bending is at the center of an A-tract and that upon modification of the 3′ adenine with (+)-CC-1065 this locus is moved less than 1 base pair to the 3′ side, and the bending magnitude is significantly increased. For drug bonding sequences such as 5′-AGTTA* or 5′-GATTA* (where * denotes the drug bonding site), the locus of bending is found to be between the two thymines, and the bending is focused over a 2-base-pair sequence rather than a 5-base-pair sequence, as is the case for the A-tract. An important distinction between an A-tract intrinsic bend and a (+)-CC-1065-induced bend is the effect of temperature. While, as shown previously, the magnitude of A-tract bending increases with decrease in temperature, for drug-induced bending of 5′-AGTTA* the bending magnitude increases with increased temperature. Hydroxyl-radical footprinting of the drug-modified 5′-AGTTA* sequence shows a decrease in cleavage centered around the TT sequence, which is presumably associated with a decrease in minor groove width. In a parallel study, the non-self-complementary 12-mer duplex (5′-GGCGGAGTTA*GG-3′)·(5′-CCTAACTC-CGCC-3′) (Figure 2B) and the corresponding (+)-CC-1065-modified duplex adduct were examined thoroughly by one- and two-dimensional 1H NMR and NOESY restrained molecular mechanics and dynamics calculations. Both the 12-mer duplex and the (+)-CC-1065-12-mer duplex adduct maintain an overall B-form DNA with the anti base orientation throughout in aqueous solution at room temperature. The 18C nucleotide of both the 12-mer duplex and its drug-modified adduct has an average C3′-endo sugar pucker The 12-mer duplex exhibits a unique internal motion at the 16A nucleotide, which is located to the 3′ side of the complementary partner of the covalently modified adenine, and a major kink at the 18C-19T step Following covalent bonding with (+)-CC-1065, the discontinuity around 18C is entrapped and further exaggerated. In addition, the 12-mer duplex adduct displays a compression of the minor groove at the 8T to 9T step and widening on both sides, but especially abruptly at the covalent modification site. Structurally the 12-mer duplex adduct bears many similarities to a bent DNA structure, which is intrinsically associated with A-tracts. The major drug-induced distortion on DNA is localized at the 9T and 10A step of the covalently modified strand. A truncated junction model for the drug-entrapped/induced bending of DNA is proposed, and a comparison to intrinsic A-tract bending is made. © 1993 American Chemical Society.