[¹²⁵I]-N-[(3-Azido-5-iodo)benzyl]dantrolene and [¹²⁵I]-N-{[3-Iodo-5-(3-trifluoromethyl-3H-diazirin-3-yl)]benzyl}dantrolene: photoaffinity probes specific for the physiological Ca²⁺ release from sarcoplasmic reticulum of sk

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• 作者：Hosoya ; Takamitsu ; Aoyama ; Hiroshi ; Ikemoto ; Takaaki ; Hiramatsu ; Toshiyuki ; Kihara ; Yasutaka ; et. al.
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2002
• 出版时间：November 18, 2002
• 年：2002
• 卷：12
• 期：22
• 页码：3263-3265
• 全文大小：119 K

文摘

In order to capture and identify key molecules that regulate the release of Ca²⁺ from the sarcoplasmic reticulum (SR) of skeletal muscle, we designed specific photoaffinity probes based on the structural modification of dantrolene. Thus, GIF-0082 and GIF-0276 possessing azido- and trifluoromethyldiazirinyl-benzyl groups, respectively, at the hydantoin moiety were found to have a highly selective inhibitory effect on physiological Ca²⁺ release (PCR) without affecting Ca²⁺-induced Ca²⁺ release (CICR). Successful realization of the sharp discrimination between PCR and CICR has led to the creation of [¹²⁵I]GIF-0082 and [¹²⁵I]GIF-0276, which were synthesized by substituting a stannyl group with ¹²⁵I in the corresponding phenylstannane precursors.