关键词: 环腺苷二磷酸核糖（cADPR）, Ca²⁺信号, 兰诺定（RyR）受体

Abstract: Ca²⁺ signaling is one of the most important intracellular signal transduction pathways in diverse cells. Local Ca²⁺ signals are mainly due to release from internal stores and these calcium release events are controlled by various second messengers and regulated by Ca²⁺ channel-associated proteins. Cyclic ADP-ribose (cADPR), a metabolite of NAD⁺, was discovered in 1987 and is a signaling molecule to regulate calcium mobilization via ryanodine receptors (RyR) from intracellular stores in a wide variety of biological systems. A main approach to explore the molecular mechanism of calcium release is to investigate the relationship of the structure of cADPR and cADPR analogues with their respective biological activities. In addition to the structure activity relationship, such studies result in novel antagonists and agonists which serve as the tools for mechanistic studies in the complex cellular system. This review outlines the design and discovery of structural mimics of cADPR (cIDPRE and cIDPDE) with replacement of one or both of the ribose moieties by ether bridges. Compounds of the type cIDPDE or cIDPRE may thus both be used as membrane-permeant, agonists of the cADPR/Ca²⁺ signaling system in intact cells.

Key words: Ca²⁺ signaling, cyclic adenosine diphosphate ribose (cADPR), ryanodine receptor (RyR)