Abstract |
PEGylation can improve the protein efficacy by prolonging serum half-life and reducing proteolytic sensitivity and immunogenicity. However, PEGylation may decrease the bioactivity of a protein by interfering with binding of its substrate or receptors. Here, staphylokinase (SAK), a thrombolysis agent for therapy of myocardial infarction, was mono-PEGylated at the C-terminus of SAK far from its bioactive domain. Phenyl, propyl, and amyl moieties were used as linkers between SAK and polyethylene glycol (PEG), respectively. Flexible propyl and amyl linkers lead to loose conformation. In contrast, rigid and hydrophobic phenyl linker induces dense PEG conformation that can extensively shield most domains adjacent to C-terminus (e.g., the antigen epitopes and proteolytic sites) of SAK and inefficiently shield its bioactive domain. As compared with loose PEG conformation, dense PEG conformation is more efficient to maintain the bioactivity, increase the plasma half-life, and decrease the proteolytic sensitivity and immunogenicity of the PEGylated SAK.
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Authors | Xiaoying Xue, Dongxia Li, Jingkai Yu, Guanghui Ma, Zhiguo Su, Tao Hu |
Journal | Biomacromolecules
(Biomacromolecules)
Vol. 14
Issue 2
Pg. 331-41
(Feb 11 2013)
ISSN: 1526-4602 [Electronic] United States |
PMID | 23301655
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3-maleimidohexanoic acid N-hydroxysuccinimide ester
- Caproates
- Succinimides
- m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester
- Polyethylene Glycols
- N-(gamma-maleimidobutyryloxy)succinimide
- Metalloendopeptidases
- PEGylated staphylokinase SY161
- auR protein, Staphylococcus aureus
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Topics |
- Animals
- Caproates
(chemistry)
- Circular Dichroism
- Hydrophobic and Hydrophilic Interactions
- Male
- Metalloendopeptidases
(chemistry)
- Myocardial Infarction
(drug therapy)
- Polyethylene Glycols
(chemistry)
- Protein Structure, Tertiary
- Proteolysis
- Rats
- Rats, Sprague-Dawley
- Succinimides
(chemistry)
- Surface Plasmon Resonance
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