G. Moyna et al., Detection of nascent polyproline II helices in solution by NMR in synthetic insect kinin neuropeptide mimics containing the X-Pro-Pro-X motif, J PEPT RES, 53(3), 1999, pp. 294-301
The conformations of three synthetic peptide analogs containing the dPro-dP
ro-dXaa motif (dXaa=dThr, dGlu, dAsn) in aqueous solution were studied by a
combination of NMR and molecular modeling simulations. The three compounds
were identified from a random D-amino acid tripeptide library on the basis
of their ability to either mimic or block the diuretic activity of neurope
ptides of the insect kinin family. TOCSY and ROESY correlations, as well as
abnormal secondary chemical shifts for protons on the D-proline residues w
ere employed to obtain conformational ensembles consistent with the experim
ental NMR data for the three analogs using an in vacuo simulated annealing
protocol. Similar secondary structures were found for the three molecules a
fter refinement, in agreement with the similarities observed between their
NMR spectra. Unrestrained molecular dynamics simulations with explicit wate
r representation indicate that the structural motifs found in vacuo are sta
ble in aqueous solution. The three analogs can be considered initiators of
right-handed poly D-proline II helices, mirror images of the poly L-proline
II left-handed helical motifs normally found in proline-rich proteins. The
role of these secondary folds on binding of the analogs to the kinin recep
tors is discussed.