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Corrination mitigates peptide aggregation as exemplified for Glucagon
Amber Liles1, Nancy Cham1, Morgan L Opp1
1Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States.
Peptides
|December 13, 2023
Summary
Corrination of glucagon using vitamin B12 precursor improves stability and reduces aggregation. This novel approach enhances glucagon
Area of Science:
- Biochemistry
- Pharmacology
- Drug Development
Background:
- Pharmaceutical development of glucagon is hindered by poor solubility, stability, and aggregation.
- These challenges limit its efficacy in treating acute hypoglycemia.
Purpose of the Study:
- To develop stable and soluble glucagon conjugates.
- To assess the efficacy and potency of these modified glucagon analogs.
Main Methods:
- Glucagon was conjugated with dicyanocobinamide (corrination).
- Chemical stability and aggregate formation were assessed using specific assays.
- Functional activity was measured via cAMP FRET assay at the human glucagon receptor.
Main Results:
- Corrinated glucagon analogs showed significantly improved chemical stability and reduced aggregation compared to native glucagon.
- Corrinated conjugate 5 demonstrated a 6.6-fold increased potency and maintained agonism after agitation.
- Native glucagon exhibited a 165-fold reduction in potency after agitation.
Conclusions:
- Corrination effectively mitigates peptide aggregation and enhances chemical stability.
- This strategy yields a more stable and potent glucagon analog for potential therapeutic use.
- The findings present a promising approach for developing improved peptide-based therapeutics.
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