Discovery of novel inhibitors for human intestinal maltase: virtual screening in a WISDOM environment and in vitro evaluation.

Abstract:

:Human intestinal maltase (HMA) is an α-glucosidase that hydrolyses α-1,4-linkages from the non-reducing end of malto-oligosaccharides. HMA is an important target to discover of new drugs for the treatment of type 2 diabetes. In this study, 308,307 compounds were virtually screened with HMA using Autodock 3.0.5 in a WISDOM production environment to discover novel inhibitors. The 42 top-scoring free binding energy compounds, representing 17 groups containing potential hydrogen bonding with key residues in the active site pocket of HMA, were tested in vitro for their inhibitory activities against recombinant HMA expressed from Pichia pastoris. Compounds 17 and 18 were competitive inhibitors exclusively for HMA without any in vitro inhibition for human pancreatic α-amylase. The K(i) values were 20 μM for both compound 17 and 18.

journal_name

Biotechnol Lett

journal_title

Biotechnology letters

authors

Nguyen TT,Ryu HJ,Lee SH,Hwang S,Cha J,Breton V,Kim D

doi

10.1007/s10529-011-0675-8

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

2185-91

issue

11

eissn

0141-5492

issn

1573-6776

journal_volume

33

pub_type

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