Abstract

A comprehensive interdisciplinary group composed of synthetic chemists, biochemists, virologists, biophysical chemists, pharmacologists and primate biologists, based upon preliminary data presented herein, propose novel structures to be used for control of human immunodeficiency viruses (HIV) infections. Preliminary data on potential anti-HIV agents which include porphyrins, metalloporphyrins, heteropolyarenes, aryl diimides and aryl diamidines are described in Projects 1-3 of this proposal. These anti-retroviral agents and the new compounds proposed for synthesis will be fully evaluated, through the Biological Core and Project 4, involving a rational progression starting with in vitro screens and including biophysical, biochemical, pharmacological and toxicological investigations concluding with in vivo assessments employing mouse and nonhuman primate models. Our group will be able to provide a comprehensive approach to developing new, effective anti-HIV agents by synthesis of new compounds, by determination of antiviral activity in cell culture and in animal models, and by biochemical and pharmacological evaluation of the effects of these compounds on both the host and the virus.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01AI027196-01
Application #
3547169
Study Section
(SRC)
Project Start
1988-09-30
Project End
1991-08-31
Budget Start
1988-09-30
Budget End
1989-08-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Georgia State University
Department
Type
Schools of Arts and Sciences
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302

  Publications

Patterson, S E; Coxon, J M; Strekowski, L (1997) Intercalation of ethidium and analogues with nucleic acids: a molecular orbital study. Bioorg Med Chem 5:277-81
Wilson, W D; Ratmeyer, L; Zhao, M et al. (1996) Design and analysis of RNA structure-specific agents as potential antivirals. J Mol Recognit 9:187-96
Strekowski, L; Gulevich, Y; Baranowski, T C et al. (1996) Synthesis and structure-DNA binding relationship analysis of DNA triple-helix specific intercalators. J Med Chem 39:3980-3
Shi, P Y; Brinton, M A; Veal, J M et al. (1996) Evidence for the existence of a pseudoknot structure at the 3' terminus of the flavivirus genomic RNA. Biochemistry 35:4222-30
Ding, D; Grayaznov, S M; Lloyd, D H et al. (1996) An oligodeoxyribonucleotide N3'--> P5' phosphoramidate duplex forms an A-type helix in solution. Nucleic Acids Res 24:354-60
Rajagopalan, P; Wudl, F; Schinazi, R F et al. (1996) Pharmacokinetics of a water-soluble fullerene in rats. Antimicrob Agents Chemother 40:2262-5
Zhao, M; Ratmeyer, L; Peloquin, R G et al. (1995) Small changes in cationic substituents of diphenylfuran derivatives have major effects on the binding affinity and the binding mode with RNA helical duplexes. Bioorg Med Chem 3:785-94
Yao, S; Wilson, W D (1995) 1D and 2D 1H NMR studies on bisantrene complexes with short DNA oligomers. Sci China B 38:1462-72
Wilson, W D; Mizan, S; Tanious, F A et al. (1994) The interaction of intercalators and groove-binding agents with DNA triple-helical structures: the influence of ligand structure, DNA backbone modifications and sequence. J Mol Recognit 7:89-98
Ratmeyer, L; Vinayak, R; Zhong, Y Y et al. (1994) Sequence specific thermodynamic and structural properties for DNA.RNA duplexes. Biochemistry 33:5298-304

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