Is β-homo-proline a pseudo-γ-turn forming element of β-peptides? An IR and VCD spectroscopic study on Ac-β-HPro-NHMe in cryogenic matrices and solutions

Phys Chem Chem Phys. 2010 Nov 7;12(41):13603-15. doi: 10.1039/c0cp00145g. Epub 2010 Sep 20.

Abstract

In order to test the pseudo-γ-turn forming capability of β-homo-proline (β(3)-HPro) 2-[(2S)-1-acetylpyrrolidin-2-yl]-N-methylacetamide (Ac-β(3)-HPro-NHMe) was synthesized and its potential energy landscape was investigated by infrared (IR) and vibrational circular dichroism (VCD) spectroscopy combined with density functional calculations. Based upon a comparison between experimental and computed spectra three different pseudo-γ-turn-like trans conformers and a cis conformer were identified in low-temperature Ar and Kr matrices. The computations in agreement with the observations reveal that, in contrast to its α-Pro analogue, the room-temperature abundance of the cis conformer is significant, falling above 10% in the isolated phase. Furthermore, solution-phase vibrational spectra and computations show that the cis conformer is predominant in polar solvents. This result indicates that β(3)-HPro is significantly less apt to form pseudo-γ-turns when compared to the γ-turn forming tendency of α-proline. The present study also shows that the interpretation of solution-phase VCD spectra of flexible molecules should be done with extra caution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Peptides / chemistry*
  • Proline / analogs & derivatives*
  • Proline / chemistry
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry*
  • Solutions / chemistry*
  • Spectrophotometry, Infrared

Substances

  • Peptides
  • Pyrrolidines
  • Solutions
  • Proline
  • homoproline