Pharmacoperoness作为一种新的治疗方法：体外鉴定和生物活性分子体内验证

Title:Pharmacoperones as a New Therapeutic Approach: In Vitro Identification and In vivo Validation of Bioactive Molecules

Volume: 17 Issue: 13

Author(s): Alfredo Ulloa-Aguirre, P. Michael Conn

Affiliation:

关键词: 构象病，促性腺激素释放激素受体，促性腺激素释放激素，促性腺功能低下，错误折叠的受体，药物分子伴侣，Pharmacoperones

摘要: In many conformational diseases caused by protein mutations, the intracellular traffic of the misfolded protein is compromised, leading to reduced or abolished function of the affected protein. Pharmacoperones (from “pharmacological chaperones”) are compounds that enter cells and serve as a molecular scaffold to aid misfolded mutant proteins to fold properly and adopt a stable, low-energy native conformation compatible with proper intracellular trafficking. The use of pharmacoperones represents the most promising therapeutic approach to treat misfolding disorders. This class of drugs has succeeded, in vitro and in vivo, in rescuing function of mutant, misfolded proteins, including enzymes, membrane receptors and ion channels. Here we describe the strategies to rescue function of misfolded G protein-coupled receptors, mainly of the gonadotropin-releasing hormone receptor, which has served as a valuable model for the development of pharmacoperone drugs and to better understand how this class of particular compounds is sensed by the target protein to correct routing, expression and function.

Cite this article as:

Alfredo Ulloa-Aguirre, P. Michael Conn , Pharmacoperones as a New Therapeutic Approach: In Vitro Identification and In vivo Validation of Bioactive Molecules, Current Drug Targets 2016; 17 (13) . https://dx.doi.org/10.2174/1389450117666160307143345