ja037822r_si_001.pdf (384.19 kB)
Cyclic Amidine Sugars as Transition-State Analogue Inhibitors of Glycosidases: Potent Competitive Inhibitors of Mannosidases
journal contribution
posted on 2004-02-25, 00:00 authored by Marie-Pierre Heck, Stéphane P. Vincent, Brion W. Murray, François Bellamy, Chi-Huey Wong, Charles MioskowskiA series of monocyclic glycoamidines bearing different exocyclic amine, alcohol, or alkyl
functionalities and bicyclic amidines derived from d-glucose and d-mannose were synthesized and tested
as inhibitors of various glycosidases. All the prepared compounds demonstrated good to excellent inhibition
toward glycosidases. In particular, the biscationic d-mannoamidine 9b bearing an exocyclic ethylamine
moiety proved to be a selective competitive inhibitor of α- and β-mannosidases (Ki = 6 nM) making it the
most potent inhibitor of these glycosidases reported to date. A favorable B2,5 boat conformation might explain
the selectivity of mannosidase inhibition compared to other glycosidases.