Activated Sugars for Drug Discovery

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43GM079004-01
Agency Tracking Number: GM079004
Amount: $100,231.00
Phase: Phase I
Program: SBIR
Awards Year: 2006
Solicitation Year: 2006
Solicitation Topic Code: N/A
Solicitation Number: PHS2006-2
Small Business Information
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (312) 997-2150
Business Contact
Phone: (312) 997-2150
Research Institution
DESCRIPTION (provided by applicant): 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, a new technology, glycorandomization, has been developed, which is a chemoenzymatic method of attaching sugars to natural production aglycons. With this method, a combination of a kinase and nucleotide transferase is 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, because it can be used to produce a library of natural product molecules that are differentially glycosylated. Our proposal is intended to continue the development of this technology by creating a library of activated sugars to feed into it. Specifically, we intend to 1) expand the substrate range of the kinase GalK on selected L-sugars using directed evolution, 2) couple the kinase and transferase reaction, and 3) demonstrate the gram-scale synthesis of an activated sugar. 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. 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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