Inhibition of Human α-Amylases By Synthetic 63-O-Benzyl-and 63-O-β-D-Galactosyl Maltotrionolactones

Abstract

ABSTRACT Maltooligosaccharides were transformed into both endo-modified oligosaccharidonolactones as substrate analogue inhibitors for human α-amylases. p-Nitrophenyl 65-O-benzyl-α-maltopentaoside (1) and p-nitrophenyl 65-O-β-D- galactosyl-α-malto-pentaoside (11), which have been synthesized as substrates for human α-amylases in serum, were selectively hydrolyzed by specific α-amylases to afford 63-O-benzyl maltotriose (8) and 63-O-β-D-galactosyl maltotriose (10), respectively. Both the modified oligomers were chemically oxidized to 63-O-benzyl maltotrionolactone (6) and 63-O-β-D-galactosyl maltotrionolactone (7), respectively. Compound 6, which is a strong competitive inhibitor, had K i values of 2.8 and 9.6 x 10−6M for human salivary α-amylase (HSA) and human pancreatic α-amylase (HPA), respectively. On the other hand, the inhibition activity of 7 was about ten times less than 6. These results indicated that the 6-O-substituted hydrophobic benzyl group enhances the binding with enzymes, whereas the corresponding hydrophilic 6-O-β-D-galactosyl substituted product weakens binding.