Journal of Medicinal Chemistry p. 720 - 725 (1993)
Update date:2022-08-04
Topics:
Gour-Salin
Lachance
Plouffe
Storer
Menard
Epoxysuccinyl dipeptide analogs of E-64 (R-EpsLeuPro-R') (Figure 1) have been synthesized with the carboxylate group on the epoxide ring either free (R = OH) or converted to an ester or an amide (R = EtO or i-BuNH) and the C- terminal amino acid proline either blocked (R' = OBzl) or free (R' = OH). These compounds were used to investigate the recently reported selectivity of this type of inhibitor for the lysosomal cysteine protease cathepsin B. It was shown that derivatization of the carboxylate on the epoxide ring confers selectivity for cathepsin B over papain only when it is combined to a dipeptidyl moiety with a free negatively charged C-terminal residue. It is proposed that this selectivity reflects interactions with histidine residues on a loop located in the primed subsites of cathepsin B which provides a positively charged anchor for the C-terminal carboxylate group of the inhibitor. The primed subsite loop of cathepsin B is not found in other cysteine proteases of the papain family and offers a unique template for designing selectivity in cysteine protease inhibitors.
View MoreOren Hydrocarbons (Qingdao) Co., Ltd.
Contact:+86-532-68607667-801
Address:Room 3 # 302, No.9 Qingyun Road, Qingdao, China
Xi'an Kaixiang Photoelectric Technology Co., Ltd
website:http://www.kxmaterials.com/
Contact:86-29-15991651477
Address:Building 6, Biopharmaceutical Industry R&D Cluster Base, No. 16, Caotang 4th Road, Caotang Science and Technology Industrial Base, High-tech Zone, Xi'an City, Shaanxi Province, China
Shanghai Rainbow Chemistry Co., Ltd.
Contact:+86-21-64968086-5815/5812
Address:3rd floor, Building 7, 251 Faladi Road, Zhangjiang Hi-Tech Park, Pudong District, Shanghai, P.R. China
Zhejiang Haizhou Pharmaceutical Co., Ltd.
website:https://www.haizhoupharma.com/
Contact:+86-576-88221016
Address:No. 19, Donghai 5th Avenue, Yanhai Industrial Zone, Linhai, Zhejiang, China
SHENYANG COMEBOARD TECHNOLOGY CO., LTD
Contact:+86-24-25724626
Address:Room2210,Tianbao International Building,No.8-1 Weigong South Street,Tiexi District,Shenyang,China
Doi:10.1021/jo01351a053
(1961)Doi:10.1021/ja01443a015
(1921)Doi:10.1016/S0040-4039(00)71307-4
(1976)Doi:10.1021/jm00294a037
(1971)Doi:10.1016/j.tetlet.2011.02.083
(2011)Doi:10.1016/S0040-4020(02)01536-3
(2003)