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Abstract

Abstract: DESCRIPTION (provided by applicant):Perhaps the most striking difference between fungal cells and human cells is that fungal cells are encased in a wall that protects them from a hostile external environment. The cell wall plays a dynamic role in all aspects of fungal physiology. The fact that human cells lack a cell wall and the underlying biosynthetic and regulatory machinery to make the wall, suggests that drugs targeting cell-wall synthesis and assembly will be safe and specific antifungals. Current treatments include Amphotericin B and a variety of azoles that inhibit membrane-sterol biosynthesis. Unfortunately, Amphotericin B is toxic to humans and clinical resistance to azoles is increasing. These observations underscore the clear need for new antifungals. In this Phase I SBIR application, we propose to develop a novel screen that targets an essential step in fungal cell-wall assembly, namely, the extracellular anchorage of GPI-class mannoproteins. This will be accomplished in two specific aims: 1). Development of a screen to detect inhibitors of GPI-mannoprotein anchoring into the cell wall; 2). Screening of extracts for inhibitors using the assay developed in Aim One. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

Thesaurus Terms:
antifungal agent, drug design /synthesis /production, drug discovery /isolation, fungal protein, glycosylphosphatidylinositol, mannose, phospholipid inhibitor
aquatic organism, drug screening /evaluation
enzyme linked immunosorbent assay, high throughput technology

Institution:	MYCOLOGICS, INC.
	12635 E MONTVIEW BLVD
	AURORA, CO 80010
Fiscal Year:	2002
Department:
Project Start:	15-FEB-2002
Project End:	14-FEB-2003
ICD:	NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG:	ZRG1