application): The long-term goal of this research is to develop novel anti-biological threat agents using combinatorial methods. The specific objectives of this program are the development of novel anti-smallpox agents. The main projects involve: preparation of libraries of drug-like molecules by high-throughput, parallel synthesis methods, and combinatorial biosynthesis for testing in high-throughput screens. The targets include vaccinia topoisomerase and H1-phosphatase. This project will utilize the following methods: (1) organic synthesis, both in solution and on the solid phase, and combinatorial chemistry; (2) microbial molecular genetics, combinatorial biosynthesis and natural product fermentation; and (3) viral molecular genetics, heterologous protein expression, in vitro enzyme assays, and antiviral assays in tissue culture.
| Nishizawa, Tomoyasu; Gruschow, Sabine; Jayamaha, Don-Hema E et al. (2006) Enzymatic assembly of the bis-indole core of rebeccamycin. J Am Chem Soc 128:724-5 |
| Pirrung, Michael C; Pansare, Sunil V; Sarma, Koushik Das et al. (2005) Combinatorial optimization of isatin-beta-thiosemicarbazones as anti-poxvirus agents. J Med Chem 48:3045-50 |
| Nishizawa, Tomoyasu; Aldrich, Courtney C; Sherman, David H (2005) Molecular analysis of the rebeccamycin L-amino acid oxidase from Lechevalieria aerocolonigenes ATCC 39243. J Bacteriol 187:2084-92 |
| Pirrung, Michael C; Sarma, Koushik Das (2004) Multicomponent reactions are accelerated in water. J Am Chem Soc 126:444-5 |
| Magarvey, Nathan A; Keller, Jessica M; Bernan, Valerie et al. (2004) Isolation and characterization of novel marine-derived actinomycete taxa rich in bioactive metabolites. Appl Environ Microbiol 70:7520-9 |
| Sohn, Jungsan; Kiburz, Brendan; Li, Zhitao et al. (2003) Inhibition of Cdc25 phosphatases by indolyldihydroxyquinones. J Med Chem 46:2580-8 |
| Pirrung, Michael C; Liu, Hao (2003) Modular, parallel synthesis of an illudinoid combinatorial library. Org Lett 5:1983-5 |
| Pirrung, M C; Pansare, S V (2001) Trityl isothiocyanate support for solid-phase synthesis. J Comb Chem 3:90-6 |
