Specific, covalent binding of an azidoretinoid to cellular retinoic acid-binding protein

Two C(5)-azido substituted aromatic retinoids were evaluated as photoaffinity probes for studying the mechanism of retinoid action. The secondary azide 1 and the tertiary azide 2 were equipotent with the parent C(5)-geminal-dimethyl substituted aromatic retinoid 3 in stimulating F9-cell differentiation. Both azides bound covalently to cellular retinoic acid-binding protein upon photolysis, but the secondary azide was twice as efficient, likely because of lesser steric hindrance. The covalent binding of azide 1 was specific, since it was inhibited by retinoic acid. Thus substitution of a photolabile group onto aromatic retinoids does not abolish biological activity and affinity for cellular retinoic acid-binding protein.