Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs. Issue 6 (10th March 2016)

• Record Type: Journal Article
• Authors: Nieto-Garcia, Olaia; Wratil, Paul R.; Nguyen, Long D.; Böhrsch, Verena; Hinderlich, Stephan; Reutter, Werner; Hackenberger, Christian P. R.
• Is Part Of: Chemical science. Volume 7:Issue 6(2016:Jun.)
• Page Start: 3928
• Page End: 3933
• Publication Date: 2016-03-10
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5sc04082e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Synthetically accessible C6-analogs of N -acetylmannosamine (ManNAc) were tested as potential inhibitors of the bifunctional UDP- N -acetylglucosamine-2-epimerase/ N -acetylmannosamine kinase (GNE/MNK), the key enzyme of sialic acid biosynthesis. Abstract : Synthetically accessible C6-analogs of N -acetylmannosamine (ManNAc) were tested as potential inhibitors of the bifunctional UDP- N -acetylglucosamine-2-epimerase/ N -acetylmannosamine kinase (GNE/MNK), the key enzyme of sialic acid biosynthesis. Enzymatic experiments revealed that the modification introduced at the C6 saccharide position strongly influences the inhibitory potency. A C6-ManNAc diselenide dimer showed the strongest kinase inhibition in the low μM range among all the substrates tested and successfully reduced cell surface sialylation in Jurkat cells.