Rigid linker peptides improve the stability and anti-inflammation effect of human serum albumin and α-melanocyte-stimulating hormone fusion proteins.
Biotechnol J
; 19(3): e2300502, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38479996
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alpha-MSH
/
Serum Albumin, Human
Limits:
Humans
Language:
En
Journal:
Biotechnol J
/
Biotechnol. j. (Internet)
/
Biotechnology journal (Internet)
Journal subject:
BIOTECNOLOGIA
Year:
2024
Document type:
Article
Country of publication:
Alemania