A frame shifted disulfide bridged analogue of angiotensin II Original Research Article

N-(2-Mercaptoethyl)glycine [NMGly] was incorporated into the 3 and 5 positions of angiotensin II and oxidized to give the corresponding cyclized disulfide c[NMGly3,5]Ang II. The binding affinity to the angiotensin II receptor (AT1) of this conformationally constrained analogue, which is related to the potent Ang II agonist c[Hcy3,5]Ang II, was examined. The analogue had no affinity to the AT1 receptor. Theoretical conformational analysis was performed to compare the conformational characteristics of model compounds of c[Hcy3,5]Ang II and the frame shifted analogue c[NMGly3,5]Ang II in an attempt to explain the lack of affinity.