Recombinant Peptide Production Platform Coupled with Site-Specific Albumin Conjugation Enables a Convenient Production of Long-Acting Therapeutic Peptide.
albumin conjugation
recombinant therapeutic peptide
serum half-life extension
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
16 Apr 2020
16 Apr 2020
Historique:
received:
24
03
2020
revised:
10
04
2020
accepted:
14
04
2020
entrez:
23
4
2020
pubmed:
23
4
2020
medline:
23
4
2020
Statut:
epublish
Résumé
The number of therapeutic peptides for human treatment is growing rapidly. However, their development faces two major issues: the poor yield of large peptides from conventional solid-phase synthesis, and the intrinsically short serum half-life of peptides. To address these issues, we investigated a platform for the production of a recombinant therapeutic peptide with an extended serum half-life involving the site-specific conjugation of human serum albumin (HSA). HSA has an exceptionally long serum half-life and can be used to extend the serum half-lives of therapeutic proteins and peptides. We used glucagon-like-peptide 1 (GLP-1) as a model peptide in the present study. A "clickable" non-natural amino acid-p-azido-l-phenylalanine (AzF)-was incorporated into three specific sites (V16, Y19, and F28) of a GLP-1 variant, followed by conjugation with HSA through strain-promoted azide-alkyne cycloaddition. All three HSA-conjugated GLP-1 variants (GLP1_16HSA, GLP1_19HSA, and GLP1_28HSA) exhibited comparable serum half-lives
Identifiants
pubmed: 32316169
pii: pharmaceutics12040364
doi: 10.3390/pharmaceutics12040364
pmc: PMC7238188
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : National Research Foundation of Korea
ID : 2019R1A2C1084910
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