Trifluoromethylthiolation of tryptophan and tyrosine derivatives : a tool for enhancing the local hydrophobicity of peptides

Gregorc, Jure (avtor), Lensen, Nathalie (avtor), Chaume, Grégory (avtor), Iskra, Jernej (avtor), Brigaud, Thierry (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: aromatic compounds, hydrophobicity, monomers, peptides, proteins, reaction products
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: Str. 13169-13177
• Številčenje: Vol. 88, iss. 18
• PID: 20.500.12556/RUL-152234
• UDK: 547.1-32-304.2:66.095.253
• ISSN pri članku: 0022-3263
• DOI: 10.1021/acs.joc.3c01373
• COBISS.SI-ID: 171743491
• Datum objave v RUL: 13.11.2023

Gradivo je del revije

• Naslov: Journal of organic chemistry
• Skrajšan naslov: J. org. chem.
• Založnik: American Chemical Society
• ISSN: 0022-3263
• COBISS.SI-ID: 235287

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: aromatske spojine, hidrofobnost, monomeri, peptidi, proteini, reakcijski produkti