Trifluoromethylthiolation of Tryptophan and Tyrosine Derivatives: A Tool for Enhancing the Local Hydrophobicity of Peptides.
The Journal of organic chemistry(2023)
摘要
The incorporation of fluorinated groups into peptides significantly affects their biophysical properties. We report herein the synthesis of Fmoc-protected trifluoromethylthiolated tyrosine (CFS-Tyr) and tryptophan (CFS-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 CFS-analogues of biologically active monoamines. To prove the concept, Fmoc-(CFS)Tyr and -Trp were incorporated into the endomorphin-1 chain () 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 CFS-containing amino acids for the rational design of bioactive peptides.
更多查看译文
关键词
peptides,tyrosine derivatives,local hydrophobicity,tryptophan
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要