Investigation on PEGylation strategy of recombinant human interleukin-1 receptor antagonist.
Although PEGylation is a potential approach to prolong the half-lives and reduce the dosing frequency of therapeutic proteins, conjugation behaviors of polymer have pivotal effects on the remaining bioactivities of the derivatives. In this study, the PEGylation strategy of recombinant human interleukin-1 receptor antagonist was investigated. The random conjugation of polyethylene glycol to amino groups on the protein resulted in a severe loss of activity and only retained 9.8% of the activity. In contrast, the PEGylation at the thiol groups had moderate effects on the bioactivity of protein and 40% of activity was conserved. The results suggested that the thiol-target PEGylation was more beneficial for IL-1ra.
Yu
Pengzhan
P
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080, China.
Zheng
Chunyang
C
Chen
Jing
J
Zhang
Guifeng
G
Liu
Yongdong
Y
Suo
Xiaoyan
X
Zhang
Guicai
G
Su
Zhiguo
Z
D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008301:Maleimides / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D004952:Esters; D053590:Interleukin 1 Receptor Antagonist Protein; D008301:Maleimides; D011994:Recombinant Proteins; C043592:maleimide; D011092:Polyethylene Glycols