C₁₂‐Helix Development in (αγ)<i>_n</i> Sequences – Spectroscopic Characterization of Boc–[Aib–γ⁴(<i>R</i>)Val]–OMe Oligomers

Abstract

Abstract The solution conformations of the αγ‐hybrid oligopeptides Boc–[Aib–γ 4 ( R )Val] n –OMe ( n = 1–8) in organic solvents have been probed by NMR, IR, and CD spectroscopic methods. In the solid state, this peptide series favors C 12 ‐helical conformations, which are backbone‐expanded analogues of 3 10 helices in α‐peptide sequences. NMR studies of the six‐ ( n = 3) and 16‐residue ( n = 8) peptides reveal that only two NH protons attached the N‐terminus residues Aib(1) and γ 4 ( R )Val(2) are solvent‐exposed. Sequential N i H–N i +1 H NOEs characteristic of local helical conformations are also observed at the α residues. IR studies establish that chain extension leads to a large enhancement in the intensities of the hydrogen‐bonded NH stretching bands (3343–3280 cm –1 ), which suggest elongation of intramolecularly hydrogen‐bonded structures. The development of C 12 ‐helical structures upon lengthening of the αγ sequence is supported by the NMR and IR observations. The CD spectra of the (αγ) n peptides reveal a negative maximum at ca. 206 nm and a positive maximum at ca. 192 nm, spectral feature that are distinct from those of 3 10 helices in α‐peptides.