Gillies Elizabeth R, Fréchet Jean M J
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, CA 94720-1460, USA.
J Am Chem Soc. 2002 Nov 27;124(47):14137-46. doi: 10.1021/ja028100n.
The design and preparation of new polyester dendrimer, poly(ethylene oxide) hybrid systems for drug delivery and related therapeutic applications, are described. These systems consist of two covalently attached polyester dendrons, where one dendron provides multiple functional handles for the attachment of therapeutically active moieties, while the other is used for attachment of solubilizing poly(ethylene oxide) chains. By varying the generation of the dendrons and the mass of the poly(ethylene oxide) chains, the molecular weight, architecture, and drug loading can be readily controlled. The "bow-tie" shaped dendritic scaffold was synthesized using both convergent and divergent methods, with orthogonal protecting groups on the periphery of the two dendrons. Poly(ethylene oxide) was then attached to the periphery of one dendron using an efficient coupling procedure. A small library of eight carriers with molecular weights ranging from about 20 kDa to 160 kDa were prepared and characterized by various techniques, confirming their well-defined structures.
本文描述了用于药物递送及相关治疗应用的新型聚酯树枝状大分子与聚环氧乙烷杂化体系的设计与制备。这些体系由两个共价连接的聚酯树枝状分子组成，其中一个树枝状分子提供多个用于连接治疗活性部分的功能手柄，而另一个则用于连接增溶聚环氧乙烷链。通过改变树枝状分子的代数和聚环氧乙烷链的质量，可以很容易地控制分子量、结构和药物负载量。使用收敛法和发散法合成了“领结”形树枝状支架，两个树枝状分子的外围带有正交保护基团。然后采用高效偶联程序将聚环氧乙烷连接到一个树枝状分子的外围。制备了一个包含八个载体的小型文库，其分子量范围约为20 kDa至160 kDa，并通过各种技术对其进行了表征，证实了它们明确的结构。
