Trifluoromethylthiolation of tryptophan and tyrosine derivativesGregorc, Jure (Avtor) Lensen, Nathalie (Avtor) Chaume, Grégory (Avtor) Iskra, Jernej (Avtor) Brigaud, Thierry (Avtor) aromatic compoundshydrophobicitymonomerspeptidesproteinsreaction productsThe incorporation of fluorinated groups into peptides significantly affects their biophysical properties. We report herein the synthesis of Fmoc-protected trifluoromethylthiolated tyrosine (CF$_3$S-Tyr) and tryptophan (CF$_3$S-Trp) analogues on a gram scale (77–93% yield) and demonstrate their use as highly hydrophobic fluorinated building blocks for peptide chemistry. The developed methodology was successfully applied to the late-stage regioselective trifluoromethylthiolation of Trp residues in short peptides (66–80% yield) and the synthesis of various CF$_3$S-analogues of biologically active monoamines. To prove the concept, Fmoc-(CF$_3$S)Tyr and -Trp were incorporated into the endomorphin-1 chain (EM-1) and into model tripeptides by solid-phase peptide synthesis. A remarkable enhancement of the local hydrophobicity of the trifluoromethylthiolated peptides was quantified by the chromatographic hydrophobicity index determination method, demonstrating the high potential of CF$_3$S-containing amino acids for the rational design of bioactive peptides.20232023-11-13 14:47:50Članek v reviji152234UDK: 547.1-32-304.2:66.095.253ISSN pri članku: 0022-3263DOI: 10.1021/acs.joc.3c01373COBISS_ID: 171743491sl