Solubility of peptides in trichloroacetic acid (TCA) solutions. Hypothesis on the precipitation mechanism

Int J Pept Protein Res. 1989 Sep;34(3):166-76. doi: 10.1111/j.1399-3011.1989.tb00227.x.


The assessment of proteolysis levels is often achieved by global quantification of the peptides soluble at different TCA concentrations, but little information is available on the features of this precipitation mechanism. Peptic, tryptic and chymotryptic digests of alpha s1, beta, and kappa caseins have been prepared and fractionated by RP-HPLC and each isolated peptide was identified. Each digest was precipitated by adding TCA to different final concentrations (2, 4, 8, and 12%). The soluble fraction was analysed by RP-HPLC. Relationships have been searched between the properties of 75 peptides obtained in this way, and their solubilities in TCA. The best correlation was found with the peptide retention time in RP-HPLC, which can be regarded as the experimental measure of peptide hydrophobicity. We concluded that TCA, by interacting with peptides, induces an increase of the hydrophobicity of peptides which can lead to aggregation through hydrophobic interactions.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Chemical Phenomena
  • Chemistry, Physical
  • Hydrogen-Ion Concentration
  • Molecular Sequence Data
  • Molecular Weight
  • Peptides / analysis*
  • Solubility
  • Structure-Activity Relationship
  • Trichloroacetic Acid*


  • Peptides
  • Trichloroacetic Acid