Journal of Pharmaceutical Sciences p. 122 - 126 (1989)
Update date:2022-09-26
Topics:
Bundgaard
Moss
Various N-acyl derivatives and N-Mannich bases of the model compound L-pyroglutamyl benzylamide were synthesized to assess their suitability as prodrug forms for the N-terminal pyroglutamyl residue occurring in several peptides, with the aim of improving peptide delivery characteristics. Whereas pyroglutamyl benzylamide was rapidly hydrolyzed by pyroglutamyl aminopeptidase, the N-acyl derivatives and N-Mannich bases (N-aminomethyl derivatives) were totally resistant to cleavage by the enzyme. On the other hand, these derivatives are readily bioreversible, the conversion to the parent pyroglutamyl amide taking place either by spontaneous hydrolysis at physiological pH, as demonstrated for the N-Mannich bases, or by plasma enzymes, as shown for the N-acyl derivatives. The results suggest that by appropriate N-acylation or N-aminomethylation it may be feasible to protect pyroglutamyl-containing peptides against cleavage by pyroglutamyl aminopeptidase and to obtain a release of the parent peptide in the organism, hence improving the delivery characteristics of such peptides.
View MoreFeiyang Biotechnology Co., Ltd.
Contact:+86-533-7866339
Address:Qilu Chemistry Park, 200m north of Management Community Building of Park
Jiangsu Taihu New Materials Holding Co., Ltd
Contact:+86-519-86160108
Address:Xueyan Town, Changzhou City, Jiangsu Province, 213169, China
Rugao Jinling Chemical Co., Ltd.(expird)
Contact:0086-513-68005586
Address:Lianluo new village huangshi town Rugao city Jiangsu Province.
Nanjing lanbai chemical Co.,Ltd.
Contact:+86-25-85499326
Address:Room 908, 9F Taiyue Building,No.285 Heyan Road
Shaanxi Lighte Optoelectronics Material Co., Ltd.
Contact:+86-29-88320728-622/619/620
Address:No.55 INDUSTRY ROAD 2,XI'AN NATIONAL CIVIL AEROSPACE INDUSTRIAL PARK.XI'AN China 710065.
Doi:10.1016/S0040-4039(01)80327-0
(1989)Doi:10.1007/BF00953419
(1988)Doi:10.1080/10426500802417950
(2009)Doi:10.1271/bbb.90221
(2009)Doi:10.1055/s-0029-1218152
(2009)Doi:10.1002/jhet.4156
(2021)