Synthesis and biological activities of a photoaffinity probe for vasotocin and oxytocin receptors.

The present study describes the synthesis and biological activities of the photoreactive vasotocin analog 1-deamino[8-lysine(N epsilon-4-azidobenzoyl)] vasotocin ([Mpa1, Lys(N epsilon-4-azidobenzoyl)8]vasotocin). The analog was obtained by introducing the photoreactive aryl azido group at the epsilon-amino group of Lys8 in [Mpa1, Lys8]-vasotocin, which was synthesized by the solid phase method. In the isolated toad urinary bladder the photoaffinity analog of vasotocin retained hydroosmotic activity in the absence of u.v.-light. After irradiation the osmotic water flow across the bladder wall increased. Moreover, the water permeability remained high during repeated periods of washout, suggesting that the analog formed covalent complexes with vasotocin receptors in the toad bladder. In the rat uterotonic assay the photoreactive vasotocin analog was without photoactivation a mild agonist. These studies suggest that the photoaffinity analog of vasotocin might be useful for the isolation of vasotocin receptors in low vertebrates and oxytocin receptors in mammals.