title: Osmolyte effects on helix formation in peptides and the stability of coiled-coils.
abstract: The ability of several naturally occurring substances known as osmolytes to induce helix formation in an alanine-based peptide have been investigated. As predicted by the osmophobic effect hypothesis, the osmolytes studies here do induce helix formation. Trimethylamine-N-oxide (TMAO) is the best structure-inducing osmolytes investigated here, but it is not as effective in promoting helix formation as the common cosolvent trifluoroethanol (TFE). We also provide a semiquantitative study of the ability of TMAO to induce helix formation and urea, which acts as a helix (and protein) denaturant. We find that on a molar basis, these agents are exactly counteractive as structure inducing and unfolding agents. Finally, we extend the investigations to the effects of urea and TMAO on the stability of a dimeric coiled-coil peptide and find identical results. Together these results support the tenets of the osmophobic hypothesis and highlight the importance of the polypeptide backbone in protein folding and stability.
authors.affiliation: Department of Medical Biochemistry & Genetics, Center for Advanced Biomolecular Research, Texas A&M University, College Station 77843-1114, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Celinski
authors.forename: J Martin
authors.initials: JM
authors.lastname: Scholtz
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004268:DNA-Binding Proteins; D019281:Dimerization; D016350:Leucine Zippers / Q000187:drug effects*; D008744:Methylamines / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D011489:Protein Denaturation; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary / Q000187:drug effects; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D014270:Trifluoroethanol / Q000494:pharmacology*; D014508:Urea / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D008744:Methylamines; D029701:Saccharomyces cerevisiae Proteins; D014270:Trifluoroethanol; D014508:Urea; D011494:Protein Kinases; C005855:trimethyloxamine; D000409:Alanine