Tao, L. u., Shi, D., Sun, D., Han, H., & Hurley, L. H. (2005). Design, synthesis and biological activity of cationic porphyrins bearing mixed 3-quinolyl and 4-pyridyl meso groups. Journal of China Pharmaceutical University, 36(5), 393-397.
Abstract:
Aim: To search for the potent telomerase inhibitors with structures of cationic porphyrins to improve the interactions between G-quadruplex and porphyrins by systematically varying the meso substituents. Methods: Porphyrins bearing mixed 3-quinolyl/4-pyridyl meso groups were synthesized using the Adler-Longo method by condensation of aldehydes with pyrrole, and then followed by methylation and ion exchange. The compounds were tested for the telomerase inhibitory activity and c-Myc inhibitory activity. Results: All compounds were found to be potent and approximately equivalent in terms of their ability to inhibit the action of telomerase in a cell-free assay. Compound 4 had the best inhibitory activity on c-Myc. Conclusion: Cationic porphyrins would be the potential anticancer candidates.
Zewail-Foote, M., Li, V., Kohn, H., Bearss, D., Guzman, M., & Hurley, L. H. (2004). Erratum: The inefficiency of incisions of ecteinascidin 743-DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent (Chemistry and Biology 8 (1033-1049)). Chemistry and Biology, 11(2), 283-.
Zewail-Foote, M., & Hurley, L. H. (1999). Ecteinascidin 743: A minor groove alkylator that bends DNA toward the major groove. Journal of Medicinal Chemistry, 42(14), 2493-2497.
PMID: 10411470;Abstract:
The ecteinascidins (Ets), which are natural products derived from marine tunicates, exhibit potent antitumor activity. Of the numerous Ets isolated, Et 743 is presently being evaluated in phase II clinical trials. Et 743 binds in the minor groove of DNA and alkylates N2 of guanine. Although structurally similar to saframycin, which exhibits poor activity in cellular assays, Et 743 has shown good efficacy as an antitumor agent. In this study, DNA structural distortions induced by Et 743 were examined to provide insight into the molecular basis for the antitumor activity of Et 743. Electrophoretic mobility shifts of ligated oligomers containing site-directed adducts were used to examine the extent and direction of the Et 743-induced bend. Surprisingly, we find that Et 743 bends DNA toward the major groove, which is a unique feature among DNA-interactive agents that occupy the minor groove.
González, V., & Hurley, L. H. (2010). The C-terminus of nucleolin promotes the formation of the c-MYC G-quadruplex and inhibits c-MYC promoter activity. Biochemistry, 49(45), 9706-9714.
PMID: 20932061;PMCID: PMC2976822;Abstract:
Nucleolin, the most abundant nucleolar phosphoprotein of eukaryotic cells, is known primarily for its role in ribosome biogenesis and cell proliferation. It is, however, a multifunctional protein that, depending on the cellular context, can drive either cell proliferation or apoptosis. Our laboratory recently demonstrated that nucleolin can function as a repressor of c-MYC transcription by binding to and stabilizing the formation of a G-quadruplex structure in a region of the c-MYC promoter responsible for controlling 85-90% of c-MYC's transcriptional activity. In this study, we investigate the structural elements of nucleolin that are required for c-MYC repression. The effect of nucleolin deletion mutants on the formation and stability of the c-MYC G-quadruplex, as well as c-MYC transcriptional activity, was assessed by circular dichroism spectropolarimetry, thermal stability, and in vitro transcription. Here we report that nucleolin's RNA binding domains 3 and 4, as well as the arginine-glycine-glycine (RGG) domain, are required to repress c-MYC transcription. © 2010 American Chemical Society.
Ostrander, J. M., Hurley, L. H., McInnes, A. G., Smith, D. G., Walter, J. A., & Wright, J. L. (1980). Proof for the biosynthetic conversion of L-[indole- 15N]tryptophan to [10- 15N]anthramycin using ( 13C, 15N) labelling in conjunction with 13C-NMR and mass spectral analysis. Journal of Antibiotics, 33(10), 1167-1171.