C_(12)-Helix development in (αγ)_n sequences - Spectroscopic characterization of Boc-[Aib-γ~4(R)Val]-OMe oligomers

摘要

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 _iH-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.