Rigid linker peptides improve the stability and anti-inflammation effect of human serum albumin and α-melanocyte-stimulating hormone fusion proteins
© 2024 Wiley-VCH GmbH..
The anti-inflammatory effect of α-melanocyte-stimulating hormone (α-MSH) in the central nervous system (CNS) has been reported for 40 years. However, the short half-life of α-MSH limits its clinical applications. The previous study has shown that a fusion protein comprising protein transduction domain (PTD), human serum albumin (HSA), and α-MSH extends the half-life of α-MSH, but its anti-inflammatory effect is not satisfactory. In this study, optimization of the structures of fusion proteins was attempted by changing the linker peptide between HSA and α-MSH. The optimization resulted in the improvement of various important characteristics, especially the stability and anti-inflammatory bioactivity, which are important features in protein medicines. Compared to the original linker peptide L0, the 5-amino-acid rigid linker peptide L6 (PAPAP) is the best option for further investigation due to its higher expression (increased by 6.27%), improved purification recovery (increased by 60.8%), excellent thermal stability (Tm = 83.5°C) and better inhibition in NF-κB expression (increased by 81.5%). From this study, the significance of the design of linker peptides in the study of structure-activity relationship of fusion proteins was proved.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Biotechnology journal - 19(2024), 3 vom: 17. März, Seite e2300502 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yiyao [VerfasserIn] |
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| Links: |
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| Themen: |
α-MSH |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 15.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/biot.202300502 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369697030 |
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| 245 | 1 | 0 | |a Rigid linker peptides improve the stability and anti-inflammation effect of human serum albumin and α-melanocyte-stimulating hormone fusion proteins |
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| 520 | |a The anti-inflammatory effect of α-melanocyte-stimulating hormone (α-MSH) in the central nervous system (CNS) has been reported for 40 years. However, the short half-life of α-MSH limits its clinical applications. The previous study has shown that a fusion protein comprising protein transduction domain (PTD), human serum albumin (HSA), and α-MSH extends the half-life of α-MSH, but its anti-inflammatory effect is not satisfactory. In this study, optimization of the structures of fusion proteins was attempted by changing the linker peptide between HSA and α-MSH. The optimization resulted in the improvement of various important characteristics, especially the stability and anti-inflammatory bioactivity, which are important features in protein medicines. Compared to the original linker peptide L0, the 5-amino-acid rigid linker peptide L6 (PAPAP) is the best option for further investigation due to its higher expression (increased by 6.27%), improved purification recovery (increased by 60.8%), excellent thermal stability (Tm = 83.5°C) and better inhibition in NF-κB expression (increased by 81.5%). From this study, the significance of the design of linker peptides in the study of structure-activity relationship of fusion proteins was proved | ||
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| 650 | 4 | |a α-MSH | |
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| 700 | 1 | |a Li, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Xueyan |e verfasserin |4 aut | |
| 700 | 1 | |a Ullah, Inam |e verfasserin |4 aut | |
| 700 | 1 | |a Uddin, Shahab |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jiatao |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Runjie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, MeiZhu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hongyu |e verfasserin |4 aut | |
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