Gas-phase helical peptides mimic solution-phase behavior

J Am Chem Soc. 2014 Oct 8;136(40):14173-83. doi: 10.1021/ja507298e. Epub 2014 Sep 23.

Abstract

In solution, α-helices are stabilized at the termini by a variety of different capping interactions. Study of these interactions in the gas phase provides a unique means to explore the intrinsic properties that cause this stabilization. Evidence of helical and globular conformations is presented here for gas-phase, doubly charged peptides of sequence XAnK, wherein X is D, N, Q, or L. The relative abundance of the helical conformation is found to vary as a function of peptide length and the identity of the first amino acid, consistent with solution phase studies that have looked at the identity of the first amino acid. The N-terminal, b ion fragments of the doubly charged precursor peptides are shown to form helical and globular conformations. The stability of the helical fragments is examined as a function of fragment length, N-terminal amino acid, precursor conformation, and the activation energy used to generate the fragment. At lower collision energies, helical b ions preferentially form, particularly from helical precursors. The abundance of the helical b ion population is observed to dramatically decrease for NAn and DAn b ions smaller than the b10; simulations suggest this feature is due to the b10 having two complete turns of the helix, while the b9 and smaller ions have only a partial second turn, suggesting the b10 is the lower limit for stable helical conformations in b ions. Use of higher collision energies promotes the formation of globular structures in the b ions. This characteristic is attributed to increased conformational dynamics and subsequently improved proton transfer kinetics from the b ion's C-terminal oxazolone ring to the N-terminus.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Gases*
  • Molecular Dynamics Simulation
  • Peptides / chemistry*
  • Protein Stability
  • Protein Structure, Secondary
  • Solutions

Substances

  • Gases
  • Peptides
  • Solutions