[Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization]
>>Published online before print August 16, 2005
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0503270102
Chemistry
Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization
( carbohydrate | natural product | sugar )
Joseph M. Langenhan *, Noël R. Peters , Ilia A. Guzei , F. Michael Hoffmann , and Jon S. Thorson *¶
*Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, and University of Wisconsin National Cooperative Drug Discovery Group Program, School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, WI 53705; Keck University of Wisconsin Comprehensive Cancer Center Small Molecule Screening Facility, K6/569, 600 Highland Avenue, Madison, WI 53705; and X-Ray Crystallography Laboratory, Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706
Edited by Kyriacos C. Nicolaou, The Scripps Research Institute, La Jolla, CA, and approved June 24, 2005 (received for review April 20, 2005)
Glycosylated natural products are reliable platforms for the development of many front-line drugs, yet our understanding of the relationship between attached sugars and biological activity is limited by the availability of convenient glycosylation methods. When a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation is used, the glycorandomization of digitoxin leads to analogs that display significantly enhanced potency and tumor specificity and suggests a divergent mechanistic relationship between cardiac glycoside-induced cytotoxicity and Na+/K+-ATPase inhibition. This report highlights the remarkable advantages of glycorandomization as a powerful tool in glycobiology and drug discovery.<<
Should come back in six months and link the full text version; looks like an interesting technology.
Cheers, Tuck |
