Activated Sugars for Drug Discovery

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$773,902.00
Award Year:
2009
Program:
SBIR
Phase:
Phase II
Contract:
2R44GM079004-02A1
Agency Tracking Number:
GM079004
Solicitation Year:
2009
Solicitation Topic Code:
n/a
Solicitation Number:
PHS2009-2
Small Business Information
ZUCHEM, INC.
ZUCHEM, INC., 2225 W. Harrison St., CHICAGO, IL, 60612
Hubzone Owned:
Y
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
126677041
Principal Investigator:
RYAN WOODYER
(312) 997-2150
RWOODYER@ZUCHEM.COM
Business Contact:
GINA BERARDESCO
(312) 997-2150
ginab@zuchem.com
Research Institution:
n/a
Abstract
DESCRIPTION (provided by applicant): The overall goal of this proposal is to create a robust one pot, in vitro, multi-gram scale synthesis of activated sugars for drug discovery and biochemical research purposes. Natural product glycosylation is vital for the discovery of new pharmaceutical compounds. While it has been recognized for some time that many biologically active natural products owe much of their therapeutic properties to their glycosylation diversity, methods for creating further diversity for drug discovery have been difficult to develop. One of the challenges is that the modified and rare sugars needed for creating diversity are unavailable or extremely difficult to make, and that the sugars need to be chemically activated in order to transfer them to the core natural product molecule. However, new technology has been developed where a chemoenzymatic method is used to attach sugars to natural production aglycons. With this method, a combination of a kinase and nucleotide transferase are needed to form the specific activated sugar and finally a glycosyltransferase is used to transfer the sugar to an appropriate aglycon core. This technology is valuable for drug discovery, as it can be used to produce a library of differentially glycosylated natural product molecules. The Phase II research of this project will continue the improvements in the enzymes needed for this process, including engineering a greater substrate range. The research will then focus on coupling the best enzymes, ATP/NTP regeneration, product recovery, process scale-up and creating novel antibiotic derivatives as a demonstration of the developed technology. PUBLIC HEALTH RELEVANCE: This project is aimed toward developing a method for making a variety of activated sugars for drug discovery purposes. These sugars can used to make derivatives of natural products with new therapeutic properties, for example, antibiotics that are effective against antibiotic-resistant bacteria.

* information listed above is at the time of submission.

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