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Fermentation initiated antibiotic synthesis

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI060249-01A2
Agency Tracking Number: AI060249
Amount: $137,162.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: PHS2005-2
Timeline
Solicitation Year: 2005
Award Year: 2005
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
PROMILIAD BIOPHARMA, INC
Alberton, MT 59820
United States
DUNS: N/A
HUBZone Owned: Unavailable
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 STEPHEN BERGMEIER
 (740) 517-8462
 BERGMEIS@OHIO.EDU
Business Contact
Phone: (406) 884-0022
Research Institution
N/A
Abstract

DESCRIPTION (provided by applicant): This Phase I Small Business Technology Transfer study between Promiliad Biopharma Inc. and Ohio University is focused on a clear prototype demonstration of REBACS, the core technology of Promiliad Biopharma. REcombinant Biotechnology Assisted Combinatorial Synthesis (REBACS) is the use of synthetic and/or genetic approaches to the construction of high complexity, high diversity compound libraries that serve as a superior starting point for biological activity screening programs. We have been particularly interested in the application of REBACS for the production of libraries of new macrolide antibiotic compounds. Our overall objective is to prepare new macrolide antibiotics that overcome bacterial resistance mechanisms. We can do this by using REBACS to generate highly diverse macrolactone components. Modifications of the macrolactone have been demonstrated to be effective. The major limitation in modifications to the macrolactone is the current need to work with a glycosylated fermentation product as the primary precursor. Much more extensive modifications to the macrolactone could be envisaged if a desosamine mimetic was found. Our first priority, therefore, is to discover such a desosamine mimetic by analysis of a library of mimetics coupled to the proven pikromycin aglycon, pikronolide. Our approach is divided into 2 phases targeted both at the macrolactone and the sugar portions of the macrolide. We envisage an overall strategy wherein genetic manipulation of the antibiotic biosynthesis genes will first generate a new macrolide structure that is optimized not for biological activity, but for ease of chemical diversification. The base upon which this overall approach stands is the assumption that the sugar mimetics that we will use will provide biologically active new macrolides. This Phase I STTR project is focused on demonstrating the first 2 steps of our program: Preparation of small molecule sugar mimetics and conjugation of the sugar mimetics to a standard, proven macrolide aglycon (pikronolide) and obtain compounds with antibacterial activity.

* Information listed above is at the time of submission. *

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