Potent chemical chaperone compounds for GM1-gangliosidosis: N-substituted (+)-conduramine F-4 derivatives

Shinichi Kuno; Katsumi Higaki; Atsushi Takahashi; Eiji Nanba; Seiichiro Ogawa

doi:10.1039/C4MD00270A

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Potent chemical chaperone compounds for G_M1-gangliosidosis: N-substituted (+)-conduramine F-4 derivatives†

Shinichi Kuno,*^a Katsumi Higaki,*^b Atsushi Takahashi,^a Eiji Nanba^b and Seiichiro Ogawa^c

Author affiliations

* Corresponding authors

^a Central Research Laboratories, Hokko Chemical Industry, Co., Ltd., 2165 Toda, Atsugi, 243-0023 Japan
E-mail: kuno-s@hokkochem.co.jp
Fax: +81-46-228-0164

^b Division of Functional Genomics, Research Center for Bioscience and Technol., Fac. of Medicine, Tottori University, 86 Nishi-cho, Yonago, 683-8503 Japan
E-mail: kh4060@med.tottori-u.ac.jp
Fax: +81-859-386470

^c Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-Ku, Yokohama, 223-8522 Japan

Abstract

The development of second-generation valienamine-type chemical chaperones for G_M1-gangliosidosis is described. Several N-substituted (+)-conduramine F-4 derivatives were designed as novel chemical chaperones based on a lead chaperone compound, N-octyl-4-epi-β-valienamine, to decrease the inhibitory activity while increasing the enzyme enhancement activity. Among the derivatives synthesized during this study, a conduramine derivative with an N-cyclohexylmethyl group has demonstrated significant enhancement of R201C mutated β-galactosidase activity.

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Article information

DOI: https://doi.org/10.1039/C4MD00270A
Article type: Concise Article
Submitted: 23 Jun 2014
Accepted: 03 Nov 2014
First published: 04 Nov 2014

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Med. Chem. Commun., 2015,6, 306-310

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Potent chemical chaperone compounds for G_M1-gangliosidosis: N-substituted (+)-conduramine F-4 derivatives

S. Kuno, K. Higaki, A. Takahashi, E. Nanba and S. Ogawa, Med. Chem. Commun., 2015, 6, 306 DOI: 10.1039/C4MD00270A

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