The conformational features of Pam-Lys(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5
)-Ser(6)-Pro(7)-Phe(8)-Arg(9)-OH (PKD) and Pam-Gly(-1)-Lys(0)-Arg(1)-Pro(2)
-Pro(3)-Gly(4)-Phe(5-)Ser(6)-Pro(7)-Phe(8)-Arg(9)-OH (PGKD), the Pam-Lys an
d Pam-Gly-Lys analogues of bradykinin have been determined by high-resoluti
on NMR in a zwitterionic lipoid environment. Radical-induced relaxation of
the H-1 NMR signals was used to probe the topological orientation of the pe
ptides with respect to the zwitterionic lipid interface. The radical-induce
d relaxation and molecular dynamics (MD) data indicated that the palmitic a
cid and N-terminal amino acid residues embed into the micelles, while the r
est of the polypeptide chain is closely associated with the water-micelle i
nterface. Throughout the entire nuclear Overhauser effect restrained MD sim
ulation, a nonideal type I beta -turn was observed in the C-terminus of PKD
between residues 6 and 9, and a gamma -turn was observed in the C-terminus
of PGKD between residues 6 and 7. Therefore, the additional glycine has a
dramatic effect on the structural preferences of the biologically important
C-terminus, an effect brought about by the interaction with the lipid envi
ronment. These structural features are correlated to the biological activit
y at the bradykinin B2 receptor. (C) 2001 John Wiley & Sons, Inc.