Premium
Solution conformations of bradykinin antagonists modified with CαCα cyclized nonaromatic residues
Author(s) -
Sikorska Emilia,
RodziewiczMotowidŁo Sylwia
Publication year - 2008
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1009
Subject(s) - chemistry , peptide , bradykinin , isomerization , stereochemistry , radius of gyration , residue (chemistry) , nuclear magnetic resonance spectroscopy , peptide bond , two dimensional nuclear magnetic resonance spectroscopy , biochemistry , organic chemistry , receptor , catalysis , polymer
The conformations of four BK antagonists, [ D ‐Arg 0 , Hyp 3 , Thi 5 , D ‐Phe 7 , Acc 8 ]BK ( 1 ), Aaa[ D ‐Arg 0 , Hyp 3 , Thi 5 , D ‐Phe 7 , Acc 8 ]BK ( 2 ), [ D ‐Arg 0 , Hyp 3 , Thi 5, 8 , Apc 7 ]BK ( 3 ), and Aaa[ D ‐Arg 0 , Hyp 3 , Thi 5, 8 , Apc 7 ]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 βII‐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 Å and is by ca 1.5 Å lower than that of the remaining analogs. With peptide 4 , the ST‐turn of type I within the Ser 6 ‐Thi 8 fragment was found. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.