C-10-O-EQ-N-(4-AZIDO-5-(125)IODO SALICYLOYL)-BETA-ALANYL-BETA ALANYL RYANODINE (AZ-BETA-AR), A NOVEL PHOTO-AFFINITY LIGAND FOR THE RYANODINE BINDING-SITE

A high affinity, photoactivatable, radio-iodinated ligand for the ryanodine binding site(s) of the sarcoplasmic reticulum calcium-release channel, C-10-O(e)-N-(4-azido-5-iodo-125 salicyloyl)-beta-alanyl-beta-alanyl ryanodine (Az-betaAR), was synthesized at a specific activity of 1400mCi/mmol. Prepared by condensing the versatile synthon, N-(4-azido-5-iodo-125 salicyloyl)-beta-alanine with C-10-O(eq)-beta-alanyl ryanodine, Az-betaAR, like [H-3] ryanodine, does not demonstrate saturation binding kinetics. 127Az-betaAR exhibits an IC50 of 27.2 +/- 2 x 10(-9) M (mean +/- SD) compared to ryanodine's 6.2 +/- 0.4 x 10(-9) M for the ryanodine receptor/calcium release channel of sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle.