The interactions which take place between DNA and compounds which bind DNA are vitally important for a number of reasons including their use as chemotherapeutic agents and as artificial restriction enzymes in molecular biology and recombinant DNA investigations. A large variety of both naturally-occurring and synthetically-derived compounds with these abilities are known. Other compounds which do not cleave DNA are nevertheless valuable as anti-cancer drugs, as DNA structure probes, and as agents which can be synthetically elaborated to incorporate cleaving functionalities. Bleomycin is a particular clinically-used anti-tumor antibiotic known for its ability to chelate various metals and to bind to DNA. Cleavage of DNAs by bound activated Fe-Bleomycin is thought to involve radicals produced during the oxidation of the complex in the presence of molecular oxygen. The Co(III)-Bleomycin complex becomes selectively localized in certain types of cancer cells where it binds to the nuclear DNA. The exact modes of the binding of intercalating agents to DNA are not well- characterized, however. It is thought that bleomycin, for example, can bind to DNA in several different ways, involving both intercalation (of varying degree) and groove binding. We propose to continue our work investigating the modes of binding of certain intercalating agents into nucleotide oligomers, synthetic polynucleotides, and native DNAs in aqueous solution using a battery of vibrational spectroscopic techniques which we now have at our disposal, including Fourier transform infrared spectroscopy (FT-IR), argon-ion (Ar+) laser induced Raman spectroscopy (Raman), and near-infrared Nd+-YAG laser induced Fourier transform Raman spectroscopy (FT-Raman). We will use these techniques to observe and characterize changes which occur in the phosphate backbone as a result of interactions between DNA and the binding agents, and investigate binding modes of the intercalators to the DNA, using marker bands for the different A, B, and Z conformation to investigate conformational changes induced by the interactions. We will also use vibrational frequency shifts induced by these interactions to characterize their interaction with different functional groups in the DNA bases and to qualify the magnitude of the various interactions which take place between DNA and the binding agents, as we have done in the past. Then we will begin our investigation of the binding of Co(III)- Bleomycin under conditions of irradiation which will not promote cleavage.

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Ifere, Godwin O; Equan, Anita; Gordon, Kereen et al. (2010) Cholesterol and phytosterols differentially regulate the expression of caveolin 1 and a downstream prostate cell growth-suppressor gene. Cancer Epidemiol 34:461-71
Mariam, Yitbarek H; Musin, Ryza N (2008) Transition from moderate to strong hydrogen bonds: its identification and physical bases in the case of O-H...O intramolecular hydrogen bonds. J Phys Chem A 112:134-45
Kimbro, K Sean; Duschene, Kaitlin; Willard, Margeret et al. (2008) A novel gene STYK1/NOK is upregulated in estrogen receptor-alpha negative estrogen receptor-beta positive breast cancer cells following estrogen treatment. Mol Biol Rep 35:23-7
Chu, Qinghui; Pang, Yi (2004) Vibronic structures in the electronic spectra of oligo(phenylene ethynylene): effect of m-phenylene to the optical properties of poly(m-phenylene ethynylene). Spectrochim Acta A Mol Biomol Spectrosc 60:1459-67
Sannigrahi, Biswajit; McGeady, Paul; Khan, Ishrat M (2004) Helical poly(3-methyl-4-vinylpyridine)/amino acid complexes: preparation, characterization, and biocompatibility. Macromol Biosci 4:999-1007
Liang, Sidney; Bu, Xiu R (2002) Tertiary pentyl groups enhance salen titanium catalyst for highly enantioselective trimethylsilylcyanation of aldehydes. J Org Chem 67:2702-4
Vanderveer, Donald; Colon, Marisabel Lebron; Bu, Xiu R (2002) Crystal structure of a chiral Ni complex: (R,R)-N,N'-bis(3-t-butylsalicylidene)-1,2-cyclohexanediaminonickel(II). Anal Sci 18:1283-4
Musey, Paul I; Ibim, Sobrasua M; Talukder, Niranjan K (2002) Development of artificial blood vessels: seeding and proliferation characteristics of endothelial and smooth muscle cells on biodegradable membranes. Ann N Y Acad Sci 961:279-83
Johnson, K P; Rowe, G C; Jackson, B A et al. (2001) Novel antineoplastic isochalcones inhibit the expression of cyclooxygenase 1,2 and EGF in human prostate cancer cell line LNCaP. Cell Mol Biol (Noisy-le-grand) 47:1039-45
Chiang, C F; Okou, D T; Griffin, T B et al. (2001) Green fluorescent protein rendered susceptible to proteolysis: positions for protease-sensitive insertions. Arch Biochem Biophys 394:229-35

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