Degradable PEGylated Protein Conjugates Utilizing RAFT Polymerization.
Degradable PEGylated Protein Conjugates Utilizing RAFT Polymerization.
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DOI：
10.1016/j.eurpolymj.2015.01.025
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发表时间：
2015-04-01
影响因子：
6
通讯作者：
Maynard, Heather D.
中科院分区：
文献类型：
--
作者：
Decker, Caitlin G.;Maynard, Heather D.
关键词：
Poly(ethylene glycol) (PEG)-protein therapeutics exhibit enhanced pharmacokinetics, but have drawbacks including decreased protein activities and polymer accumulation in the body. Therefore a major aim for second-generation polymer therapeutics is to introduce degradability into the backbone. Herein we describe the synthesis of poly(poly(ethylene glycol methyl ether methacrylate)) (pPEGMA) degradable polymers with protein-reactive end-groups via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the subsequent covalent attachment to lysozyme through a reducible disulfide linkage. RAFT copolymerization of cyclic ketene acetal (CKA) monomer 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) with PEGMA yielded two polymers with number-average molecular weight (Mn) (GPC) of 10.9 and 20.9 kDa and molecular weight dispersities (Ð) of 1.34 and 1.71, respectively. Hydrolytic degradation of the polymers was analyzed by 1H-NMR and GPC under basic and acidic conditions. The reversible covalent attachment of these polymers to lysozyme, as well as the hydrolytic and reductive cleavage of the polymer from the protein, was analyzed by gel electrophoresis and mass spectrometry. Following reductive cleavage of the polymer, an increase in activity was observed for both conjugates, with the released protein having full activity. This represents a method to prepare PEGylated proteins, where the polymer is readily cleaved from the protein and the main chain of the polymer is degradable.
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影响因子：
5.5
作者：
BAILEY, WJ;NI, Z;WU, SR
通讯作者：
WU, SR
DOI：
10.1073/pnas.1006044107
发表时间：
2010-09-21
影响因子：
11.1
作者：
Gao, Weiping;Liu, Wenge;Chilkoti, Ashutosh
通讯作者：
Chilkoti, Ashutosh
影响因子：
6.2
作者：
Delplace, Vianney;Tardy, Antoine;Nicolas, Julien
通讯作者：
Nicolas, Julien
影响因子：
3.5
作者：
GARMAN, AJ;KALINDJIAN, SB
通讯作者：
KALINDJIAN, SB
影响因子：
5.5
作者：
Riachi, Carl;Schuwer, Nicolas;Klok, Harm-Anton
通讯作者：
Klok, Harm-Anton