Title | D-glyconhydroximolactams strongly inhibit alpha-glycosidases |
Publication Type | Journal Article |
Year of Publication | 1997 |
Authors | HOOS, R, VASELLA, A, RUPITZ, K, Withers, SG |
Journal | CARBOHYDRATE RESEARCH |
Volume | 298 |
Pagination | 291-298 |
Date Published | MAR 13 |
ISSN | 0008-6215 |
Abstract | It has been postulated that proton transfer to beta-glycosides by some retaining beta-glycosidases takes place in the plane of the pyranoside ring. It is now hypothesised that a similarly oriented catalytically active acidic group in alpha-glycosidases could interact with glyconolactone derivatives, provided that these are sufficiently basic to overcome the effect of a less favourable geometry by an energetically more favourable interaction. In keeping with this hypothesis, D-gluconolactone, D-gluconolactam, the tetrazole 3, and the hydroximolactone 5 are weak inhibitors of yeast alpha-glucosidase, while the hydroximolactam 6 (pK(a) = 4.8) is a mixed-type (alpha=2) strong inhibitor (K-i = 2.9 mu M). A Similar inhibition is observed for the arylcarbamoyl derivative 9, while the (methylthio)methyl derivative 10 inhibits more weakly and in a purely competitive fashion. The mannonhydroximolactam 11 strongly inhibits jack bean a-mannosidase (K-i=0.15 mu M), while the gluco analogue 6 inhibits about 80 times more weakly, illustrating the dependence upon configuration. (C) 1997 Elsevier Science Ltd. |
DOI | 10.1016/S0008-6215(96)00320-5 |