20.500.12556/RUL-152234 Trifluoromethylthiolation of tryptophan and tyrosine derivatives a tool for enhancing the local hydrophobicity of peptides The 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. aromatic compounds hydrophobicity monomers peptides proteins reaction products aromatske spojine hidrofobnost monomeri peptidi proteini reakcijski produkti true false true Angleški jezik Slovenski jezik Članek v reviji 2023-11-13 14:47:50 2023-11-13 14:47:51 2023-12-05 03:41:04 0000-00-00 00:00:00 2023 0 0 Str. 13169-13177 iss. 18 Vol. 88 15 Sep. 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 547.1-32-304.2:66.095.253 0022-3263 10.1021/acs.joc.3c01373 171743491 gregorc-et-al-2023-trifluoromethylthiolation-of-tryptophan-and-tyrosine-derivatives-a-tool-for-enhancing-the-local.pdf gregorc-et-al-2023-trifluoromethylthiolation-of-tryptophan-and-tyrosine-derivatives-a-tool-for-enhancing-the-local.pdf 1 AC8FE653C84CB916DCC36D13D29DCD25 e4e70510b31638ea6ee2125792c619a230828a63de2fc45d7b01492134493dda 859573f8-92ad-11ee-9ca9-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=178317 https://pubs.acs.org/doi/10.1021/acs.joc.3c01373 1 3d775701-822b-11ee-a249-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=177599 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0