Genetically Encoding a Lipidated Amino Acid for Extension of Protein Half-Life inâ
vivo.
Angew Chem Int Ed Engl
; 58(5): 1392-1396, 2019 01 28.
Article
en En
| MEDLINE
| ID: mdl-30474173
ABSTRACT
Protein therapeutics are increasingly used to treat various diseases, yet they often suffer from short serum half-lives. An emerging strategy to extend lifetime inâ
vivo is to attach fatty acids onto proteins to increase their binding to human serum albumin (HSA). Herein, the genetic encoding of ϵ-N-heptanoyl-l-lysine (HepoK) is reported, which introduces a fatty-acid-containing amino acid into proteins with exquisite site-specificity and homogeneity, overcoming issues associated with existing chemical conjugation methods. The expression in Eâ
.coli and purification of HepoK-incorporated glucagon-like peptide-1 (GLP1) is demonstrated. GLP1(HepoK) showed stronger binding to HSA than GLP1(WT), without impairing the stimulation of the GLP1 receptor in cells. Moreover, GLP1(HepoK) decreased blood glucose level to the same level as GLP1(WT) in mice, showing longer-lasting effects than GLP1(WT). HepoK incorporation will also be useful for investigating the function of protein lipidation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptido 1 Similar al Glucagón
/
Código Genético
/
Aminoácidos
/
Lípidos
/
Lisina
Límite:
Animals
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2019
Tipo del documento:
Article
País de afiliación:
China