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

Abstract

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 β-hairpin conformations in CDCl₃, C₆D₆ and (CD₃)₂SO, nucleated by a D-Pro-Gly Type II′ β-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 β-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)₂SO, 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 β-turn conformations. These results suggest that in short peptide sequences, the precise nature of the β-turn is critical for hairpin formation, with Type II′ β-turns being particularly effective.

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