Strategic Alkene Incorporation into Peptide Backbones to Prevent Enzymatic Hydrolysis by Evading Molecular Recognition

Key Points

• The research aims to demonstrate how replacing specific peptide bonds with alkene isosteres can enhance the stability of peptides against enzymatic degradation.
• Modification of the peptide backbone at the C-terminal region of ubiquitin
• Replacement of Gly75-Gly76 bond with alkene dipeptide isosteres
• Evaluation of resistance to hydrolysis by enzymatic assays
• Alkene dipeptide isosteres significantly increased the resistance to enzymatic hydrolysis compared to traditional peptides
• Enhanced stability observed specifically at the C-terminal region of ubiquitin