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Abstract

Abstract: DESCRIPTION (provided by applicant): This proposal outlines a novel approach towards the development of a therapeutic agent to treat anthrax infection by inhibiting the intracellular actions of lethal factor, the main virulence factor expressed in Bacillus anthracis infected organisms. While antibiotics are effective in treating early-stage anthrax infection by "wild-type" Bacillus anthracis strains, they are ineffective in treating infection at later stages, infection by antibiotic-resistant strains or infection with other modified bacteria or viruses engineered to express lethal factor. This SBIR Phase I feasibility study includes the development of screening assays (primary peptide cleavage and secondary macrophage-based cytotoxicity) for evaluation of unique metalloproteinase inhibitor libraries already synthesized at Hawaii Biotechnology Group, Inc. under a current contract from the Department of Defense. The most interesting lethal factor inhibitors derived from this study (approx. 3-20 compounds) will be optimized in Phase II according to standard pharmaceutical strategies with which we have significant experience. The resulting drug-like molecules will have efficacy in treating lethal factor delivered to the organism by "wild-type" Bacillus anthracis strains or other pathogens. In addition to the potential large commercial market for anthrax therapies, selected compounds will be tested in models for other bacteria as well as cancer and immunoinflammatory diseases.

Thesaurus Terms:
Bacillus anthracis, bioassay, drug design /synthesis /production, enzyme inhibitor, lethal gene, metalloendopeptidase
anthrax, cytotoxicity, high throughput technology, peptide library, virulence
bioterrorism /chemical warfare, cell line

Institution:	HAWAII BIOTECH, INC.
	99-193 AIEA HEIGHTS DR, STE 236
	AIEA, HI 96701
Fiscal Year:	2002
Department:
Project Start:	01-JUL-2002
Project End:	30-JUN-2003
ICD:	NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG:	ZRG1