Synthesis and Structural Stability of α-Helical Gold(I)-Metallopeptidesy

The synthesis of hexa- and dodecapeptides functionalized with two Au(I)-phosphine complexes is reported. The high stability of the Au(I)- phosphine bond allowed orthogonal peptide-protectinggroup chemistry, even when using hard Lewis acids like boron tribromide. This enabled the preparation of an Fmoc-protected lysine derivative carrying the Au(I) complex in a side chain, which was used in standard Fmoc-based solid-phase peptide synthesis protocols. Alanine and leucine repeats in the metallododecapeptide formed alpha-helical secondary structures in 2,2,2-trifluoroethanol-H2O and 1,1,1,3,3,3-hexafluoroisopropanol- H2O mixtures with high thermal stability, as shown by temperature-dependent CD spectroscopy studies.

Automated summary

The synthesis of hexa- and dodecapeptides functionalized with two Au(I)-phosphine complexes demonstrated the high stability of the Au(I)-phosphine bond, allowing orthogonal peptide-protecting-group chemistry. The metallododecapeptide formed alpha-helical secondary structures with high thermal stability in specific solvent mixtures.