Synthesis of sulfhydryl cross-linking poly(ethylene glycol)-peptides and glycopeptides as carriers for gene delivery
Synthesis of sulfhydryl cross-linking poly(ethylene glycol)-peptides and glycopeptides as carriers for gene delivery
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DOI：
10.1021/bc010070a
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发表时间：
2002-03-01
影响因子：
4.7
通讯作者：
Rice, KG
中科院分区：
文献类型：
--
作者：
Park, Y;Kwok, KY;Rice, KG
制备巯基交联聚（乙二醇）（PEG）-肽和糖肽，并测试其与质粒DNA结合时通过二硫键形成的自发聚合，产生稳定的PEG-肽和糖肽DNA缩合物。一个20个氨基酸的合成肽具有一个单一的巯基的N-末端半胱氨酸，与两个或五个内部乙酰氨基甲基（Acm）保护的半胱氨酸残基，与PEG乙烯砜或碘乙酰胺酪氨酸酰胺三触角N-聚糖反应。在RP-HPLC纯化后，通过银四氟硼酸盐除去Acm基团以产生巯基交联PEG-肽和糖肽，其通过H-1 NMR或LC-MS表征。发现巯基交联PEG-肽和糖肽与质粒DNA结合并进行二硫键交联，从而产生稳定的DNA缩合物，其具有用于体内基因递送的潜在效用。
Sulfhydryl cross-linking poly(ethylene glycol) (PEG)-peptides and glycopeptides were prepared and tested for spontaneous polymerization by disulfide bond formation when bound to plasmid DNA, resulting in stable PEG-peptide and glycopeptide DNA condensates. A 20 amino acid synthetic peptide possessing a single sulfhydryl group on the N-terminal cysteine, with two or five internal acetamidomethyl (Acm)-protected cysteine residues, was reacted with either PEG vinyl sulfone or iodoacetamide tyrosinamide triantennary N-glycan. Following RP-HPLC purification, Acm groups were removed by silver tetrafluoroborate to generate sulfhydryl cross-linking PEG-peptides and glycopeptide that were characterized by either H-1 NMR or LC-MS. Sulfhydryl cross-linking PEG-peptides and glycopeptides were found to bind to plasmid DNA and undergo disulfide cross-linking resulting in stable DNA condensates with potential utility for in vivo gene delivery.