Inhibition of β-N-acetylglucosaminidase by substituted septanose triazoles

CHED 1338

Emily Cherney1, Steve Castro, buyproduct@aol.com2, and Mark W. Peczuh, mark.peczuh@uconn.edu2. (1) Department of Chemistry, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, (2) Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269
In working toward a general understanding of protein-septanose interactions, the ability of septanose analogs to inhibit glycosidase enzymes has been explored. A key feature of the septanose analogs investigated is that they contain a non-hydrolyzable glycosidic linkage to a triazole moiety. The septanose triazoles were prepared via click chemistry using the corresponding septanosyl azide and a series of terminal alkynes. Our primary objective was to determine if unnatural seven membered ring (septanose) sugars would bind to natural proteins (enzymes). To that end, UV-based assays on various commercially available glycosidases were performed to determine if the septanose triazoles would inhibit the reaction. A preliminary screen of seen glycosidases showed that β-N-acetylglucosaminidase was inhibited. Kinetics experiments provided Ki values that ranged from 300 to 500 μM and a competitive mode of inhibition.
 

Undergraduate Research Poster Session: Medicinal
2:00 PM-4:00 PM, Monday, March 26, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007