Synthesis and pharmacological properties of TOAC-labeled angiotensin and bradykinin analogs

Angiotensin II (AngII) and bradykinin (BK) derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) spin label were synthesized by solid phase methodology. Ammonium hydroxide (pH 10, 50degreesC, 1 h) was the best means for reverting nitroxide protonation occurring during peptide cleavage. EPR spectra yielded rotational correlation times for internally labeled analogs that were nearly twice as large as those of N-terminally labeled analogs. Except for TOAC(1)-AngII and TOAC(0)-BK, which showed high intrinsic activities, other derivatives were inactive in smooth muscle preparations. These active paramagnetic analogs may be useful for conformational studies in solution and in the presence of model and biological membranes. (C) 2002 Elsevier Science Inc. All rights reserved.Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUNESP, Inst Chem, Dept Biochem, P-4800060 Araraquara, SP, BrazilUniv São Paulo, Inst Chem, Dept Biochem, BR-05513970 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilWeb of Scienc