[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 skeletal muscle

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.