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

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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.

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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.

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Authors and Affiliations

  1. School of Biological Sciences and Technology & The Research Institute for Catalysis, Chonnam National University, Gwangju, 500-757, South Korea

    Thi Thanh Hanh Nguyen, Hwa-Ja Ryu & Doman Kim

  2. Department of Pediatrics, University of California, San Diego, California, 92103, USA

    Doman Kim

  3. Korea Institute of Science and Technology Information, 335 Gwahangno, Yuseong-gu, Daejeon, 305-806, South Korea

    Se-Hoon Lee & Soonwook Hwang

  4. Department of Microbiology, College of Natural Sciences, Pusan National University, Busan, 609-735, South Korea

    Jaeho Cha

  5. LPC Clermont-Ferrand, Campus des Cézeaux, 63177, Aubière Cedex, France

    Vincent Breton

Authors
  1. Thi Thanh Hanh Nguyen
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  2. Hwa-Ja Ryu
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  3. Se-Hoon Lee
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  4. Soonwook Hwang
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  5. Jaeho Cha
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  6. Vincent Breton
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  7. Doman Kim
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Correspondence to Doman Kim.

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Nguyen, T.T.H., Ryu, HJ., Lee, SH. et al. Discovery of novel inhibitors for human intestinal maltase: virtual screening in a WISDOM environment and in vitro evaluation. Biotechnol Lett 33, 2185–2191 (2011). https://doi.org/10.1007/s10529-011-0675-8

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  • DOI: https://doi.org/10.1007/s10529-011-0675-8

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