D-glyconhydroximolactams strongly inhibit alpha-glycosidases
Hoos, R; Vasella, A; Rupitz, K; Withers, SG
| HERO ID | 4940975 |
|---|---|
| In Press | No |
| Year | 1997 |
| Title | D-glyconhydroximolactams strongly inhibit alpha-glycosidases |
| Authors | Hoos, R; Vasella, A; Rupitz, K; Withers, SG |
| Journal | Carbohydrate Research |
| Volume | 298 |
| Issue | 4 |
| Page Numbers | 291-298 |
| 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 |
| Wosid | WOS:A1997WM95700005 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Keyword | yeast alpha-glucosidase; Jack bean alpha-mannosidase; D-gluconhydroximolactam; glucosidase inhibitors |