Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins
Dipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as fu...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-04-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383513001123 |
| _version_ | 1818962370514386944 |
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| author | Jinglong Liu Yi Huan Caina Li Minzhi Liu Zhufang Shen |
| author_facet | Jinglong Liu Yi Huan Caina Li Minzhi Liu Zhufang Shen |
| author_sort | Jinglong Liu |
| collection | DOAJ |
| description | Dipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as functional activity with DPP4. However, the inhibition of their activities was reported to cause severe toxicities. Thus, the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy. To achieve this goal, we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells. In this method, we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system. The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL, respectively, and the corresponding concentrations of their substrates were both 0.2 mmol/L. This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates, which would provide valuable guidance in the development of safe DPP4 inhibitors. |
| first_indexed | 2024-12-20T12:28:15Z |
| format | Article |
| id | doaj.art-42d719960e0a433bbb44f15cb0dead4c |
| institution | Directory Open Access Journal |
| issn | 2211-3835 2211-3843 |
| language | English |
| last_indexed | 2024-12-20T12:28:15Z |
| publishDate | 2014-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-42d719960e0a433bbb44f15cb0dead4c2022-12-21T19:40:47ZengElsevierActa Pharmaceutica Sinica B2211-38352211-38432014-04-014213514010.1016/j.apsb.2013.12.007Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteinsJinglong LiuYi HuanCaina LiMinzhi LiuZhufang ShenDipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as functional activity with DPP4. However, the inhibition of their activities was reported to cause severe toxicities. Thus, the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy. To achieve this goal, we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells. In this method, we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system. The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL, respectively, and the corresponding concentrations of their substrates were both 0.2 mmol/L. This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates, which would provide valuable guidance in the development of safe DPP4 inhibitors.http://www.sciencedirect.com/science/article/pii/S2211383513001123DPP4DPP8DPP9InhibitorSelective evaluation method |
| spellingShingle | Jinglong Liu Yi Huan Caina Li Minzhi Liu Zhufang Shen Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins Acta Pharmaceutica Sinica B DPP4 DPP8 DPP9 Inhibitor Selective evaluation method |
| title | Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins |
| title_full | Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins |
| title_fullStr | Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins |
| title_full_unstemmed | Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins |
| title_short | Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins |
| title_sort | establishment of a selective evaluation method for dpp4 inhibitors based on recombinant human dpp8 and dpp9 proteins |
| topic | DPP4 DPP8 DPP9 Inhibitor Selective evaluation method |
| url | http://www.sciencedirect.com/science/article/pii/S2211383513001123 |
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