Conformation-specific spectroscopy of capped, gas-phase Aib oligomers: tests of the Aib residue as a 3-helix former.

The conformational preferences of a series of capped peptides containing the helicogenic amino acid aminoisobutyric acid (Aib) (Z-Aib-OH, Z-(Aib)-OMe, and Z-(Aib)-OMe) are studied in the gas phase under expansion-cooled conditions. Aib oligomers are known to form 3-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)-OMe are both observed to have minor conformations that exhibit dihedral angles consistent with the 3-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 3-helix. For Z-(Aib)-OMe three conformers are observed in the gas phase. Single-conformation infrared spectroscopy in both the NH stretch (Amide A) and C[double bond, length as m-dash]O stretch (Amide I) regions identifies the main conformer as an incipient 3-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 3-helices, and a dipole moment that shrinks to 5.4 D. These results show Aib to be a 3-helix former in the gas phase at the earliest stages of oligomer growth.