title: Solution conformations of bradykinin antagonists modified with Calpha-Calpha cyclized nonaromatic residues.
abstract: The conformations of four BK antagonists, [D-Arg 0, Hyp3, Thi5, D-Phe7, Acc8]BK (1), Aaa[D-Arg 0, Hyp3, Thi5, D-Phe7, Acc8]BK (2), [D-Arg 0, Hyp3, Thi5, 8, Apc7]BK (3), and Aaa[D-Arg(0), Hyp(3), Thi(5, 8), Apc7]BK (4) were studied by using 2D NMR spectroscopy and MD simulations with time-averaged (TAV) restraints. According to the results of the NMR measurements, the BK antagonists contain 7-30% of minor conformation resulting from cis/trans isomerization of the peptide bonds preceding either Pro or Hyp residues. The major conformation of each peptide possesses all peptide bonds in trans configuration. Peptides modified with the Apc residue at position 7 (peptides 3 and 4) possess a higher percentage of minor isomer. Peptide 1 exhibits the strongest vasodepressor potency among the analogs studied and as a single one forms the betaII-turn in the 2-5 fragment, which is believed to be crucial for antagonistic activity. This peptide is also the most compact. The radius of gyration (Rg) amounts to 6.9 A and is by ca 1.5 A lower than that of the remaining analogs. With peptide 4, the ST-turn of type I within the Ser6-Thi8 fragment was found.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, Gdańsk, Poland. milka@chem.univ.gda.pl
authors.forename: Emilia
authors.initials: E
authors.lastname: Sikorska
authors.forename: Sylwia
authors.initials: S
authors.lastname: Rodziewicz-Motowidło
mesh_terms: D001920:Bradykinin / Q000037:antagonists & inhibitors*; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
chemical_list: D001920:Bradykinin