Center for Education and Research on Macromolcules, University of Liège, B6a Sart-Tilman, 4000 Liège, Belgium.
Bioconjug Chem. 2012 Sep 19;23(9):1740-52. doi: 10.1021/bc200650n. Epub 2012 Aug 28.
α-Acetal, ω-alkyne poly(ethylene oxide) was synthesized as building block of glycoconjugated poly(ε-caprolactone)-graft-poly(ethylene oxide) (PCL-g-PEO) copolymers. The alkyne group is indeed instrumental for the PEGylation of a poly(α-azido-ε-caprolactone-co-ε-caprolactone) copolymer by the Huisgen's 1,3 dipolar cycloaddition, i.e., a click reaction. Moreover, deprotection of the acetal end-group of the hydrophilic PEO grafts followed by reductive amination of the accordingly formed aldehyde with an aminated sugar is a valuable strategy of glycoconjugation of the graft copolymer, whose micelles are then potential. A model molecule (fluoresceinamine) was first considered in order to optimize the experimental conditions for the reductive amination. These conditions were then extended to the decoration of the graft copolymer micelles with mannose, which is a targeting agent of dendritic cells and macrophages. The bioavailability of the sugar units at the surface of micelles was investigated by surface plasmon resonance (SPR). The same question was addressed to nanoparticles stabilized by the graft copolymer. Enzyme linked lectin assay (ELLA) confirmed the availability of mannose at the nanoparticle surface.
α-乙酰基，ω-炔基聚（氧化乙烯）被合成作为糖基化聚（ε-己内酯）-接枝-聚（氧化乙烯）（PCL-g-PEO）共聚物的结构单元。炔基对于通过 Huisgen 的 1,3 偶极环加成，即点击反应，将聚（α-叠氮基-ε-己内酯-共-ε-己内酯）共聚物的聚乙二醇化是非常重要的。此外，亲水性 PEO 接枝的缩醛端基的脱保护，以及相应形成的醛与氨基化糖的还原胺化，是糖基化接枝共聚物的一种有价值的策略，其胶束随后具有潜在的应用。首先考虑了一种模型分子（荧光胺），以优化还原胺化的实验条件。然后将这些条件扩展到用甘露糖修饰接枝共聚物胶束，甘露糖是树突状细胞和巨噬细胞的靶向剂。通过表面等离子体共振（SPR）研究了胶束表面糖单元的生物利用度。同样的问题也涉及到由接枝共聚物稳定的纳米粒子。酶联凝集素测定（ELLA）证实了纳米粒子表面甘露糖的可用性。
