Changing GLP-1’s shape prevents its breakdown while keeping its metal-binding part

Selective D-amino acid substitutions can enhance the proteolytic stability of glucagon-like peptide-1 (GLP-1) while maintaining its metal-binding capabilities.

• GLP-1 is rapidly degraded by proteases, which limits its effectiveness in biological systems.
• Stereochemical engineering through D-amino acid substitutions effectively blocks proteolysis.
• The modified GLP-1 analogue retains its ability to coordinate metal ions.
• Significant alterations to the peptide's primary structure do not compromise its metal-binding function.
• This approach shows that enzymatic stability and coordination properties can be independently optimized in peptide systems.

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