Yamazaki N, Kojima S, Bovin N V, André S, Gabius S, Gabius H J
Materials Design Laboratory, Department of Organic Materials, National Institute of Materials and Chemical Research, 1-1 Higashi, Tsukuba-City, 305, Ibaraki, Japan.
Adv Drug Deliv Rev. 2000 Sep 30;43(2-3):225-44. doi: 10.1016/s0169-409x(00)00071-5.
To minimize side effects of drugs it would be ideal to target them exclusively to those cell types which require treatment. As a means to this end prototypical cellular recognition systems pique our interest to devise biomimetic strategies. Since oligosaccharides of glycoconjugates outmatch other information-carrying biomolecules (proteins, nucleic acids) in theoretical storage capacity by far, work on the sugar code can spark off development of effective targeting devices. Conjugation of custom-made glycan epitopes to proteins or biocompatible non-immunogenic polymeric scaffolds produces neoglycoconjugates with purpose-adaptable properties. In the interplay with endogenous receptors such as lectins, suitable oligosaccharides such as histo-blood group trisaccharides as parts of neoglycoconjugates have already proven their practical applications in histopathology. Elucidation of the structure of cell lectins with currently five main families aids to tailor ligand characteristics rationally. They include the types of functional groups and their topological presentation to optimize the bimolecular binding as well as the optimal spatial clustering and spacer characteristics to exploit cooperativity. Indeed, the potent trivalent cluster glycosides designed for the C-type asialoglycoprotein receptors furnish an instructive example how to turn the theoretical guideline on ligand modification into nM-affinity. By placing emphasis on tissue lectins as targets of neoglycoconjugate-mediated drug delivery, the long-term perspective is opened to likewise test members of these families themselves for routing of therapeutic payloads, aiming at cell addressins. This review illustrates the conceivable potential which work on the sugar code with custom-made neoglycoconjugates and tissue lectins can have in store for drug delivery.
为了将药物的副作用降至最低，理想的做法是将它们专门靶向那些需要治疗的细胞类型。作为实现这一目标的手段，典型的细胞识别系统激发了我们设计仿生策略的兴趣。由于糖缀合物的寡糖在理论存储容量方面远远超过其他携带信息的生物分子（蛋白质、核酸），因此对糖密码的研究可以推动有效靶向装置的开发。将定制的聚糖表位与蛋白质或生物相容性非免疫原性聚合物支架结合，可产生具有适应性特性的新糖缀合物。在与内源性受体（如凝集素）的相互作用中，合适的寡糖（如新糖缀合物的一部分组织血型三糖）已在组织病理学中证明了其实际应用。阐明目前五个主要家族的细胞凝集素结构有助于合理调整配体特性。它们包括官能团的类型及其拓扑呈现，以优化双分子结合，以及最佳的空间聚类和间隔特性，以利用协同作用。事实上，为C型去唾液酸糖蛋白受体设计的强效三价簇状糖苷提供了一个有启发性的例子，说明如何将配体修饰的理论指导转化为纳摩尔亲和力。通过将重点放在组织凝集素作为新糖缀合物介导的药物递送的靶点上，开启了长期前景，同样可以测试这些家族的成员本身用于治疗有效载荷的递送，目标是细胞地址素。这篇综述阐述了利用定制的新糖缀合物和组织凝集素对糖密码的研究在药物递送方面可能具有的潜在可能性。
