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 -hairpin conformations in CDCl 3 , C 6 D 6 and (CD 3 ) 2 SO, nucleated by a D-Pro-Gly Type IIЈ -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 -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 (CD 3 ) 2 SO, while in CDCl 3 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 -turn conformations. These results suggest that in short peptide sequences, the precise nature of the -turn is critical for hairpin formation, with Type IIЈ -turns being particularly effective.

Stabilizing capping motif for β-hairpins and sheets

“…All of these spectroscopic features could be used as probes to determine fold population (χ F ). * Gly4 to L-Ala and D-Ala mutations (SI Appendix) had negligible effects on fold stability of Ac-WIpGKWTG-NH 2 even though these enforce type II′ and I′ turns, respectively (6,32). This indifference to turn type prompted us to view Ac-W --WTG as a general capping motif and to examine its efficacy at positions remote from the turn.…”

Strand Length-Dependent Antimicrobial Activity and Membrane-Active Mechanism of Arginine- and Valine-Rich β-Hairpin-Like Antimicrobial Peptides

“…A short two-residue loop segment ( D PG) was used to link the two-strand antiparallel ␤-sheet. D PG stabilizes the type II= ␤-turn and promotes the formation of ␤-hairpin conformations (13,30). The ␤-hairpin was further stabilized by a disulfide bridge.…”

Diastereomeric Selective Effects for Growth Inhibition of Synthesized Mini Parallel Double-Stranded Peptides on Escherichia coli and Staphylococcus aureus

“…In fluorometry, compound 21 emits a siganal at about 530 nm with an excitation wavelength of 349 nm in 85% methanol. 6 /CDCl 3 (volume ratioϭ0.2 ml/0.5 ml). However, the chemi-cal shifts of aH 1 and aH 2 of the long molecule 20a appeared at 4.50 and 4.09 ppm, respectively.…”

“…In an effort to clarify the chemical properties, functions, and stereochemistry of b-turn (or bhairpin) and antiparallel b-sheet structures, the design and synthesis of peptides have been reported by a number of research groups. [1][2][3][4][5][6] Model compounds which mimic b-sheet and b-turn structures have been shown to adopt b-hairpin structures in an aqueous solution, and hydrogen bonding can stabilize the b-turn structure. Recently, we have reported the synthesis and chemical properties of mini parallel doublestranded peptides, (L-AA 3 -L-AA 2 -L-AA 1 ) 2 -spacer(S) (AAϭ amino acids; Sϭethano-and dodecano-, etc.)…”

“…13 C-NMR (signal assignments from the spectra of C-H COSY at 500 Mz, CDCl 3 /DMSO-d 6 1 H-NMR (signal assignments from the spectra of H-H COSY at 500 MHz, CDCl 3 /DMSO-d 6 (0.5 ml/0.2 ml)) d: -L-Phe)-N,N-octane-1,8-diamine (19a 1 H-NMR (signal assignments from the spectra of H-H COSY at 500 MHz, CDCl 3 /DMSO-d 6 (0.5 ml/ 0.2 ml)) d: 1.14-1.26 (m, 8H, -CH 2 -CH 2 -ϫ2), 1. CD Measurements The CD spectra of 18a-d were measured on a JASCO J-600 spectrophotometer.…”