Stabilization of Helical Conformation in Model Peptides by 2,2,2-Trifluoroethanol: An FTIR Study

  • Wendy Barber-Armstrong
  • Mohini Sridharan
  • Sean M. Decatur
Part of the American Peptide Symposia book series (APSY, volume 7)


Despite the widespread use of TFE as a helix-stabilizing agent, the mechanism of its action is still widely debated. While mechanisms in which TFE binds to residues in the helical conformation and stabilizes the structure have been proposed [1], there is no evidence for direct interactions between TFE and hydrophobic side chains [2]. Alternatively, recent explanations of the TFE effect have focussed on the impact of TFE on the structure of water and its solvation of peptide groups. Three different mechanisms of helix stabilization by TFE involving solvation effect have been proposed. Based on studies of the effect of TFE on the conformation of alanine-rich helical peptides and intramolecular hydrogen bonding in salicylic acid, Luo and Baldwin proposed that desolvation of the backbone carbonyls in a helix strengthens intrahelical hydrogen bonding; the stronger hydrogen bonding increases the enthalpic stability of the helix versus random coil in TFE/water mixtures [3]. In studies of coiled-coil peptides, Kenstis and Sosnick have proposed that the increased solvent structure in TFE/water mixtures (as opposed to pure water) raises the energy of solvation of peptide backbone groups in the unfolded state; this indirectly enhances the stability of the helical state [4]. Recently, Cammers-Goodwin and co-workers have proposed that in pure water, there is a greater ordering of the solvent shell around the helix compared to the coil state, resulting in an unfavorable entropic change; by disrupting hydrogen bonding between the helix backbone and solvent, TFE reduces the solvent ordering which occurs upon helix formation, stabilizing the helix relative to the coil state [5].


Random Coil Solvent Shell Helical Conformation Hydrophobic Side Chain Coil State 
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Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • Wendy Barber-Armstrong
    • 1
  • Mohini Sridharan
    • 1
  • Sean M. Decatur
    • 1
  1. 1.Department of ChemistryMount Holyoke CollegeS. HadleyUSA

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