Photoaffinity labeling of the angiotensin II receptor. 3. Receptor inactivation with photolabile hormone analogs

Abstract

It has been shown that the receptor of angiotensin II (AT) in rabbit aorta strips, rat aorta, and rat stomach can be blocked specifically and irreversibly by several photolabile analogues of Sar-Arg-Val-Tyr-Val-His-Pro-Phe ([Sar1]AT) with irradiation. The effectiveness of a photolabel with light of wavelength 365 nm depends on the labeling amino acid (L-4'-nitrophenylalanine, L-4'-diazoniumphenylalanine, or L-4'-azidophenylalanine) and on its position in the peptide (replacing Tyr4 and/or Phe8). The 4'-azido)Phe-containing analogues are all good to fair photoinactivators. Their decreasing order of effectiveness is as follows: [Sar1,(4'-azido)Phe8]AT, [Sar1,(4'-azido)Phe4,8]AT, and [Sar1,(4'-azidoPhe4]AT. The (4'-nitro)Phe analogues show the opposite relation: the good ligand [Sar1,(4'-nitro)Phe8]AT is almost ineffective, but the nonligand [Sar1,(4-nitro)Phe4]AT exhibits good, specific photoinactivation. This can be explained by the existence of a different photolysis pathway for (4'-nitro)Phe: this analogue probably undergoes a multiphoton decay with a long-lived first excited state. A peptide in this state may differ in its pharmacological properties from the ground state and become a ligand.