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A new screening method based on yeast-expressed human dipeptidyl peptidase IV and discovery of novel inhibitors

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Abstract

Dipeptidyl peptidase (DPP) IV inhibitors provide a new strategy for the treatment of type 2 diabetes. Human DPP-IV gene was cloned from differentiated Caco-2 cells and expressed in Pichia pastoris. The recombinant enzyme was used in a new system for screening of DPP-IV inhibitors. By high throughput screening, a novel compound (W5188) was identified from 75,000 compounds with an IC50 of 6.5 μM. This method is highly reproducible and reliable for discovery of DPP-IV inhibitors as shown by Z′ value of 0.73 and S/N ratio of 6.89.

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Acknowledgements

We thank Dr. Jinyou Xu in Merck Co. (USA) for providing the synthetic route of INDP-2 and thank Dr. Haihong Huang and Dr. Ailin Liu in our Institute for chemical synthesis of the positive compound and technical assistance of compound library, respectively. Also, we thank Dr. Chenhui Zou in Boston, USA for his technical assistance. This work was partially supported by the Hi-Tech Research and Development (863) Program of China (2002AA27343B).

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Authors and Affiliations

  1. Department of Biosynthesis of Natural Products, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100050, China

    Chen-Xi Hu, Ke-Di Cheng & Ping Zhu

  2. Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100050, China

    Hui Huang & Zhu-Fang Shen

  3. National Centre for Drug Screening, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100050, China

    Li Zhang & Guan-Hua Du

  4. Institute and State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin, 300071, China

    You Huang

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  1. Chen-Xi Hu
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  2. Hui Huang
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Correspondence to Ping Zhu.

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Hu, CX., Huang, H., Zhang, L. et al. A new screening method based on yeast-expressed human dipeptidyl peptidase IV and discovery of novel inhibitors. Biotechnol Lett 31, 979–984 (2009). https://doi.org/10.1007/s10529-009-9963-y

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  • DOI: https://doi.org/10.1007/s10529-009-9963-y

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