β-hairpin nucleation by Pro-Gly β-turns.: Comparison of D-Pro-Gly and L-Pro-Gly sequences in an apolar octapeptide

The solution conformation of the synthetic octapeptide Boc-Leu-Val-Val-D-Pro-Gly-Leu-Val-Val-OMe 1 and Boc-Leu-Val-Val-Pro-Gly-Leu-Val-Val-OMe 2 have been investigated in organic solvents by NMR spectroscopy. Peptide 1 adopts well-defined beta-hairpin conformations in CDCl3, C6D6 and (CD3)(2)SO, nucleated by a D-Pro-Gly Type II' beta-turn, as demonstrated by the observation of characteristic nuclear Overhauser effects (NOEs) between backbone protons and solvent shielding of NH groups involved in cross-strand hydrogen bonding, Chemical shifts and coupling constants provide further support for the beta-hairpin conformation, which is consistent with the observation of a single negative circular dichroism band at 216 nm in methanol. In peptide 2, there is no characteristic interstrand NOE observed in (CD3)(2)SO, while in CDCl3 pronounced aggregation results in line broadening, The observation of a low temperature coefficient for the Leu(6)NH proton favours a population of Pro-Gly Type II beta-turn conformations. These results suggest that in short peptide sequences, the precise nature of the beta-turn is critical for hairpin formation, with Type II' beta-turns being particularly effective.