UV Resonance Raman Determination of Polyproline II, Extended 2.51-Helix, and β-Sheet Ψ Angle Energy Landscape in Poly-l-Lysine and Poly-l-Glutamic Acid

Abstract

UV resonance Raman (UVR) spectroscopy was used to examine the solution conformation of poly-l-lysine (PLL) and poly-l-glutamic acid (PGA) in their non-α-helical states. UVR measurements indicate that PLL (at pH = 2) and PGA (at pH = 9) exist mainly in a mixture of polyproline II (PPII) and a novel left-handed 2.5₁-helical conformation, which is an extended β-strand-like conformation with Ψ ≈ +170° and Φ ≈ −130°. Both of these conformations are highly exposed to water. The energies of these conformations are very similar. We see no evidence of any disordered “random coil” states. In addition, we find that a PLL and PGA mixture at neutral pH is ∼60% β-sheet and contains PPII and extended 2.5₁-helix conformations. The β-sheet conformation shows little evidence of amide backbone hydrogen bonding to water. We also developed a method to estimate the distribution of Ψ Ramachandran angles for these conformations, which we used to estimate a Ψ Ramachandran angle energy landscape. We believe that these are the first experimental studies to give direct information on protein and peptide energy landscapes.