Development of Long-Acting Human Adrenomedullin Fc-Fusion Proteins.
Biology (Basel)
; 11(7)2022 Jul 19.
Article
em En
| MEDLINE
| ID: mdl-36101452
ABSTRACT
(1) Background:
Human adrenomedullin (hAM) is a hypotensive peptide hormone that exerts powerful anti-inflammatory effects. AM also had therapeutic effects in various animal experimental models of disease. However, treatment required continuous administration as the half-life of native AM is short in blood. To resolve this, we developed four human IgG1 and IgG4 Fc-fusion proteins containing full-length hAM or hAM residues 6-52. (2)Methods:
We used mammalian cells to produce recombinant Fc-AM derivatives and tested the pharmacokinetics and biological activity of Fc-AM. (3)Results:
We developed four Fc-fusion AMs (Fc-AM), which are long-acting AM derivatives in mammalian cells. Fc-AM had a prolonged half-life in blood and retained its ability to bind to the AM1 receptor. Fc-AM (6-52) induced higher cAMP levels for the receptor than Fc-AM. After the administration of IgG1-AM (6-52) or IgG4-AM (6-52) to rats, tissue transfer to the kidney and small intestine was observed. In addition, treatment with IgG4-AM (6-52) inhibited blood pressure increase in spontaneously hypertensive rats. (4)Conclusions:
Fc-AM produced from mammalian cells can be easily prepared and might be an effective novel therapeutic agent.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Biology (Basel)
Ano de publicação:
2022
Tipo de documento:
Article