Molecular modelling of acarviosine, the pseudo-disaccharide moiety of acarbose, and other inhibitors of alpha-amylases.
Acarbose and its homologs inhibit alpha-D-glucosidases, particularly alpha-amylases. These homologs have the same core, the pseudo-disaccharide acarviosine, linked to various numbers of glucose residues. The conformations of (R)- and (S)-acarviosine have been analysed. The potential energy maps, obtained by molecular mechanics calculations, show that acarviosine is flexible and has several important minima. One low-energy form is close to the shape assumed by the acarviosine moiety when acarbose is adsorbed on the surface of glycogen phosphorylase. Another likely conformation is the same as that inferred from n.m.r. data and HSEA calculations. The results reconcile those conflicting reports. Molecular modelling of other inhibitors of alpha-amylases, such as 4-thiomaltose and moranoline, shows that these pseudo-disaccharides can fill similar volumes of conformational space.
Raimbaud
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Laboratoire de Physicochimie des Macromolécules, Institut National de la Recherche Agronomique, Nantes, France.
Buléon
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A
Pérez
S
S
D017485:1-Deoxynojirimycin; D000606:Amino Sugars / Q000737:chemistry*; D002240:Carbohydrate Sequence; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D007536:Isomerism; D008320:Maltose / Q000737:chemistry; D008432:Mathematical Computing; D008969:Molecular Sequence Data; D000516:alpha-Amylases / Q000037:antagonists & inhibitors*
D000606:Amino Sugars; C076099:acarviosine; D017485:1-Deoxynojirimycin; D008320:Maltose; D000516:alpha-Amylases; D005944:Glucosamine