Secondary Structure Characterization of Glucagon Products by Circular Dichroism and Nuclear Magnetic Resonance Spectroscopy.
Molecules
; 27(22)2022 Nov 12.
Article
en En
| MEDLINE
| ID: mdl-36431905
ABSTRACT
Glucagon, a 29-amino acid polypeptide hormone, is an essential therapeutic agent used in the emergency treatment of hypoglycemia. However, glucagon is inherently unstable in aqueous solution. While glucagon equilibrates between unordered and the secondary α-helix state in solution, it can quickly transform into a different secondary ß-sheet-rich amyloid-like fibril/oligomer structure under various conditions. Since changes in the secondary structure of glucagon can cause significant impacts, structure analysis is necessary and essential to assess the safety of the product. This study analyzed the secondary structure of glucagon products at the release and at the expiry using circular dichroism spectroscopy (CD) and 2D Nuclear Overhauser effect spectroscopy (2D NOESY). In order to also determine if structural differences exist between glucagon produced through different manufacturing processes, synthetic and recombinant glucagon products were used and compared. The CD results indicated that for all release and expired glucagon products, the structure compositions were 14 to 16% α-helix, 17 to 19% ß-strand, 14 to 15% Turn, and 53 to 54% Unordered. This was consistent with the 2D NOESY analysis which showed that both products had an approximate α-helix composition of 14 to 17%. Overall, there were no significant differences in terms of the secondary structure between synthetic and recombinant glucagon products both at the release and at the expiry.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glucagón
/
Hipoglucemia
Límite:
Humans
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos