Conformation-specific spectroscopy of capped, gas-phase Aib oligomers: tests of the Aib residue as a 310-helix former

Abstract

The conformational preferences of a series of capped peptides containing the helicogenic amino acid aminoisobutyric acid (Aib) (Z-Aib-OH, Z-(Aib)₂-OMe, and Z-(Aib)₄-OMe) are studied in the gas phase under expansion-cooled conditions. Aib oligomers are known to form 3₁₀-helical secondary structures in solution and in the solid phase. However, in the gas phase, accumulation of a macrodipole as the helix grows could inhibit helix stabilization. Implementing single-conformation IR spectroscopy in the NH stretch region, Z-Aib-OH and Z-(Aib)₂-OMe are both observed to have minor conformations that exhibit dihedral angles consistent with the 3₁₀-helical portion of the Ramachandran map (ϕ, ψ = −57°, −30°), even though they lack sufficient backbone length to form 10-membered rings which are a hallmark of the developed 3₁₀-helix. For Z-(Aib)₄-OMe three conformers are observed in the gas phase. Single-conformation infrared spectroscopy in both the NH stretch (Amide A) and CO stretch (Amide I) regions identifies the main conformer as an incipient 3₁₀-helix, having two free NH groups and two C10 H-bonded NH groups, labeled an F-F-10-10 structure, with a calculated dipole moment of 13.7 D. A second minor conformer has an infrared spectrum characteristic of an F-F-10-7 structure in which the third and fourth Aib residues have ϕ, ψ = 75°, −74° and −52°, 143°, Ramachandran angles which fall outside of the typical range for 3₁₀-helices, and a dipole moment that shrinks to 5.4 D. These results show Aib to be a 3₁₀-helix former in the gas phase at the earliest stages of oligomer growth.