Backbone-Fluorinated 1,2,3-Triazole-Containing Dipeptide Surrogates.

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Peptide Science

Background:

• The 1,2,3-triazole moiety serves as a valuable peptide bond bioisostere.
• Incorporating triazoles enhances protease resistance in peptidomimetics.
• Fluorinated triazoles offer unique properties for biomolecular design.

Purpose of the Study:

• To synthesize novel peptidomimetic building blocks featuring backbone-fluorinated 1,4-disubstituted 1,2,3-triazoles.
• To establish synthetic routes for Xaa-ψ[triazole]-F₂Gly dipeptide surrogates.
• To demonstrate the incorporation of these building blocks into a biologically relevant peptide, Leu-enkephalin.

Main Methods:

• Development of synthetic protocols for fluorinated triazole-containing dipeptide surrogates.
• Utilizing click chemistry for 1,2,3-triazole ring formation.
• Incorporation of Xaa-ψ[triazole]-F₂Gly units into Leu-enkephalin.

Main Results:

• Successful synthesis of various Xaa-Gly dipeptide surrogates as Xaa-ψ[triazole]-F₂Gly building blocks.
• Demonstrated feasibility of introducing these modified units into the Leu-enkephalin sequence.
• Established a foundation for creating protease-resistant peptide analogs.

Conclusions:

• Backbone-fluorinated 1,2,3-triazoles are effective peptide bond bioisosteres.
• The developed synthetic methods enable the creation of novel peptidomimetics.
• These peptidomimetics hold potential for developing protease-resistant therapeutic peptides.