Improving pharmacological activities of thrombopoietin mimetic peptide by genetic fusion to albumin-binding domain.
Biotechnol Lett
; 45(4): 439-448, 2023 Apr.
Article
em En
| MEDLINE
| ID: mdl-36879168
ABSTRACT
OBJECTIVE:
Thrombopoietin mimetic peptide (TMP), an analog of natural thrombopoietin, can be used to treat primary immune thrombocytopenia. However, the short half-life of TMP limits its application in clinics. The present study aimed to improve the stability and biological activity of TMP in vivo via genetic fusion to the albumin-binding protein domain (ABD).RESULTS:
TMP dimer was genetically fused to the N-terminal or C-terminal of ABD, denoted as TMP-TMP-ABD and ABD-TMP-TMP. A Trx-tag was used to improve the fusion proteins' expression levels effectively. ABD-fusion TMP proteins were produced in Escherichia coli and purified by Ni2+-NTA and SP ion exchange column. Albumin binding studies in vitro showed that the fusion proteins could effectively bind to serum albumin to extend their half-lives. The fusion proteins effectively induced platelet proliferation in healthy mice, and the platelet count was increased by more than 2.3-fold compared with the control group. The increased platelet count induced by the fusion proteins lasted 12 days compared with the control group. The increasing trend was maintained for 6 days before a decline occurred after the last injection in the fusion-protein-treated mice group.CONCLUSIONS:
ABD can effectively improve the stability and pharmacological activity of TMP by binding to serum albumin, and the ABD-fusion TMP protein can promote platelet formation in vivo.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Albumina Sérica
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article