Angiotensin II and bradykinin analogues containing the pyrrolidine-based paramagnetic amino acid POAC:biological activity and EPR structural investigation

摘要

This report initiated a structure-activity investigation of the vasoactive AII and BK analogues containing the 2,2,5,5-tetramethypyrrolidine-N-oxyl-3-amino-4-carboxylic acid(POAC)spin label.Paralleling previous studies with a piperidine-type spin probe TOAC,POAC~0-BK,POAC~3-BK and POAC~1-AII were synthesized.As the POAC chiral probe is synthesized as a mixture of two trans enantiomers(3S4S and 3R4R),the separation of both components was recently successfully achieved by Mazaleyrat's group although the absolute configuration of these two compounds are not still established.In the present report,we decided to test an alternative approach where the racemic mixture of Fmoc-POAC was coupled to AII and BK sequences expecting that further HPLC purification would separate the two peptide diastereomers of POAC~0-BK,POAC~3-BK and POAC~1-AII sequences.