ǂa ǂtool for enhancing the local hydrophobicity of peptides
Jure Gregorc (Author), Nathalie Lensen (Author), Grégory Chaume (Author), Jernej Iskra (Author), Thierry Brigaud (Author)

Abstract

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.

Keywords

aromatske spojine;hidrofobnost;monomeri;peptidi;proteini;reakcijski produkti;aromatic compounds;hydrophobicity;monomers;peptides;proteins;reaction products;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
UDC: 547.1-32-304.2:66.095.253
COBISS: 171743491 Link will open in a new window
ISSN: 0022-3263
Views: 85
Downloads: 8
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Other data

Secondary language: Slovenian
Secondary keywords: aromatske spojine;hidrofobnost;monomeri;peptidi;proteini;reakcijski produkti;
Type (COBISS): Article
Pages: str. 13169-13177
Volume: ǂVol. ǂ88
Issue: ǂiss. ǂ18
Chronology: 15 Sep. 2023
DOI: 10.1021/acs.joc.3c01373
ID: 20959969