pK(a)-Determination and Conformational Studies by NMR Spectroscopy of D-Altrose-Containing and other Pseudodisaccharides as Glycosidase Inhibitor Candidates
2012 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 1, 74-84 p.Article in journal (Refereed) Published
The pK(a) values of six amine-linked pseudodisaccharides have been determined by using an NMR-based titration method. The pK(a) varies significantly depending on the linkage position and is inversely correlated with the number of electronegative groups in the beta-position to the amino group. Four of the pseudodisaccharides contain alpha-altroside moieties, the conformations of which were determined in the protonated and neutral states, again by using NMR techniques. In the neutral state, 2-amino-2-deoxyaltrosides and 3-amino-3-deoxyaltrosides were both found to occupy C-4(1) and S-O(2) conformations. On protonation, little change in the population distribution was seen for the 3-amino-3-deoxyaltrosides, but for the 2-amino-2-deoxyaltrosides, a shift in equilibrium position towards the skew conformer (more than 80% populated) takes place, and also a small amount of the other chair conformer (i.e., C-1(4), approximately 10% populated) was observed. 3-Amino-3-deoxyaltrosides have been shown to act as glycosidase inhibitors and insights into conformational equilibria as a function of protonation state should facilitate the design of better glycosidase inhibitors based on flexible monosaccharide amines.
Place, publisher, year, edition, pages
2012. no 1, 74-84 p.
Carbohydrates, Conformation analysis, NMR spectroscopy, Protonation, Inhibitors, Enzymes
IdentifiersURN: urn:nbn:se:su:diva-76752DOI: 10.1002/ejoc.201101385ISI: 000299294000010OAI: oai:DiVA.org:su-76752DiVA: diva2:527200
FunderSwedish Research CouncilKnut and Alice Wallenberg Foundation