Pharmaceutical Research p. 1101 - 1104 (1995)
Update date:2022-07-30
Topics:
Bai
Purpose. The purpose of this study is to investigate the characteristics of pGlu-L-Dopa-Pro as a prodrug of L-Dopa. Methods. pGlu-L-Dopa-Pro and L-Dopa-Pro were synthesized using the standard procedures of peptide synthesis. The conversion of pGlu-L-Dopa-Pro to L-Dopa was studied using pyroglutamyl aminopeptidase I and prolidase. With rats as the animal model, the stability of pGlu-L-Dopa-Pro in intestinal homogenates was determined, then the transport characteristics of pGlu-L-Dopa-Pro were studied using in-situ perfusion and Ussing chambers. Results. pGlu-L-Dopa-Pro, relatively stable in intestinal homogenates and intestinal fluid, had a dimensionless permeability of 1.8 at 0.04 mM. Its intestinal permeability was significantly inhibited by 20 mM captopril, by a mixture of dipeptides, 80 mM Gly-Gly and 5 mM Gly-Pro, and by 2 mM cephradine. Further, in Ussing chambers, its mucosal to serosal permeability decreased dramatically with concentration. Conversion studies showed that pGlu-L-Dopa-Pro was degraded by pyroglutamyl aminopeptidase I, an enzyme releasing the N-terminal pyroglutamic acid, with Vmax and Km of 0.6 μmole/min/g protein and 21 mM, respectively, and that L-Dopa-Pro was degraded by prolidase with Vmax and Km of 44 μmole/min/g protein and 0.48 mM, respectively. Conclusions. This tripeptide, a potential prodrug of L-Dopa, is absorbed by the intestinal peptide transporter, is relatively stable in the gut wall, and is converted to L-Dopa by peptidases with the cleavage by pyroglutamyl aminopeptidase I to L-Dopa-Pro as the rate limiting step.
View MoreHuludao Tianqi Shengye Chemical Co.,Ltd.
Contact:0086 429 2075777
Address:Area B,Shipbuilding Industry Park,Beigang District,Huludao City,Liaoning prov.,China
Wuhan Benjamin Pharmaceutical Chemical Co.,Ltd
Contact:86-27-52341789
Address:Room 1518 B suite, optical valley time square, No 111 Guanshan Road, Hongshan District,Wuhan,Hubei Province,China.
website:http://www.antaibio.com
Contact:86-21-60939051,60939771
Address:1518#,ZHANGYANG ROAD
HENAN NEW BLUE CHEMICAL CO.,LTD
website:http://www.newbluechem.com
Contact:86-371-55170693/55170694
Address:Zhengzhou International Trade New Territory,Jinshui District,Zhengzhou ,China
Nantong LiKai Chemical Co.,Ltd
Contact:+86-513-89068669
Address:Jincheng Science Park
Doi:10.1248/cpb.6.325
(1958)Doi:10.1016/0040-4039(95)00369-N
(1995)Doi:10.1016/0957-4166(96)00068-7
(1996)Doi:10.1016/0040-4039(95)01410-J
(1995)Doi:10.1002/adsc.201801723
(2019)Doi:10.1055/s-1995-4017
(1995)