Propensity for Helix Formation in the Hydrophobic Peptides K2(LA) x (x = 6, 8, 10, 12) in Monolayer, Bulk, and Lipid-Containing Phases. Infrared and Circular Dichroism Studies

A series of hydrophobic peptides K2(LA) x (x = 6, 8, 10, 12) has been synthesized. IR and CD studies in MeOH solution are reported, along with IR studies of these species in vesicles with 1,2-dipalmitoylphosphatidylcholine, and IR Reflection−Absorption Spectroscopy (IRRAS) studies of peptide and lipid/peptide monolayer films in situ at the air/water interface. In bulk phases, the propensity toward helix formation increases with increasing chain length, there being essentially no helix in the shortest peptide, varying and concentration-dependent helical content in K2(LA)8, and >90% helix formation in both K2(LA)10 and K2(LA)12. In monolayers at the air/water interface, peptide secondary structure was inferred from both the Amide I and Amide A bands. The shortest peptide adopted an antiparallel β-sheet structure, while the remainder of the series (when spread at low surface pressure) appeared to adopt varying proportions of parallel β-sheet forms. The secondary structure adopted by K2(LA)10 and K2(LA)12 depended remarkably on the initial spreading pressure; when spread at high pressures, the molecules were α-helical. The current experiments demonstrate the unique advantages of IRRAS for evaluation of peptide conformations in situ at the air/water interface and reveal large differences in the propensity for helix formation in monolayers compared with bulk phases.