Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens GA 30602, USA.
Chemistry. 2011 Jan 17;17(3):839-46. doi: 10.1002/chem.201002052. Epub 2010 Nov 17.
Multifunctional dendrimers bearing two or more surface functionalities have the promise to provide smart drug delivery devices that can for example combine tissue targeting and imaging or be directed more precisely to a specific tissue or cell type. We have developed a concise synthetic methodology for efficient dendrimer assembly and heterobifunctionalization based on three sequential azide-alkyne cycloadditions. The methodology is compatible with biologically important compounds rich in chemical functionalities such as peptides, carbohydrates, and fluorescent tags. In the approach, a strain-promoted azide-alkyne cycloaddition (SPAAC) between polyester dendrons modified at the focal point with an azido and 4-dibenzocyclooctynol (DIBO) moiety provided dendrimers bearing terminal and TMS-protected (TMS=trimethylsilyl) alkynes at the periphery. The terminal alkynes were outfitted with azido-modified polyethylene glycol (PEG) chains or galactosyl residues by using Cu(I) -catalyzed azide-alkyne cycloadditions (CuAAC). Next, a one-pot TMS deprotection and second click reaction of the resulting terminal alkyne with azido-containing compounds gave multifunctional dendrimers bearing complex biologically active moieties at the periphery.
具有两个或多个表面官能团的多功能树突状聚合物有望提供智能药物输送装置，例如可以将组织靶向和成像结合起来，或者更精确地靶向特定的组织或细胞类型。我们已经开发了一种基于三个连续叠氮-炔环加成反应的高效树突状聚合物组装和杂双功能化的简明合成方法。该方法与富含化学官能团的生物重要化合物（如肽、碳水化合物和荧光标记物）兼容。在该方法中，通过在焦点处用叠氮和 4-二苯并环辛炔醇（DIBO）部分修饰的聚酯树突之间的应变促进的叠氮-炔环加成（SPAAC），提供了在末端和 TMS 保护（TMS=三甲基硅基）炔基处带有末端和 TMS 保护（TMS=三甲基硅基）炔基的树枝状聚合物在周边。末端炔基通过使用铜（I）催化的叠氮-炔环加成（CuAAC）用叠氮修饰的聚乙二醇（PEG）链或半乳糖基残基进行了修饰。接下来，一锅法 TMS 脱保护和所得末端炔与含叠氮化合物的第二次点击反应，得到了在周边带有复杂生物活性基团的多功能树枝状聚合物。
