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Biotechnology Letters

, 33:2185 | Cite as

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

  • Thi Thanh Hanh Nguyen
  • Hwa-Ja Ryu
  • Se-Hoon Lee
  • Soonwook Hwang
  • Jaeho Cha
  • Vincent Breton
  • Doman KimEmail author
Original Research Paper

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.

Keywords

Alpha-glucosidase Inhibitor Diabetes Human intestinal maltase Virtual screening Wisdom 

Notes

Acknowledgments

This work was partially supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2010-0021474 and No. 2009-0090025). Authors acknowledge support from FKPPL Internal Associated Laboratory for grid computing resources.

Supplementary material

10529_2011_675_MOESM1_ESM.pdf (287 kb)
Supplementary material 1 (PDF 246 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Thi Thanh Hanh Nguyen
    • 1
  • Hwa-Ja Ryu
    • 1
  • Se-Hoon Lee
    • 3
  • Soonwook Hwang
    • 3
  • Jaeho Cha
    • 4
  • Vincent Breton
    • 5
  • Doman Kim
    • 1
    • 2
    Email author
  1. 1.School of Biological Sciences and Technology & The Research Institute for CatalysisChonnam National UniversityGwangjuSouth Korea
  2. 2.Department of PediatricsUniversity of CaliforniaSan DiegoUSA
  3. 3.Korea Institute of Science and Technology InformationDaejeonSouth Korea
  4. 4.Department of Microbiology, College of Natural SciencesPusan National UniversityBusanSouth Korea
  5. 5.LPC Clermont-FerrandAubière CedexFrance

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