Native Chemical Ligation,Thiol–Ene Click: A Methodology for the Synthesis of Functionalized Peptides

Abstract

The sequential combination of native chemical ligation and thiol−ene radical chemistry (NCL-TEC) on the resulting cysteine thiol has been investigated as a methodology for rapidly accessing functionalized peptides. Three sequential cycles of native chemical ligation and subsequent thiyl radical reactions (including a free-radical-mediated desulfurization reaction) were carried out on a peptide backbone demonstrating the iterative nature of this process. The versatility of the thiyl radical reaction at cysteine was demonstrated through the introduction of a number of different side chains including an amino acid derivative, a carbohydrate group, and an alkyl azide. Conditions were developed that allowed the sequential NCL-TEC process to proceed in high yield.

Silvia Giordani

Full Professor Chair of Nanomaterials

My research interests are in the design, synthesis, and characterization of hybrid smart nanomaterials for biomedical, energy and environmental applications