Microarrays of synthetic heparin oligosaccharides
Microarrays of synthetic heparin oligosaccharides
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DOI：
10.1021/ja057584v
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发表时间：
2006-03-08
影响因子：
15
通讯作者：
Seeberger, PH
中科院分区：
文献类型：
--
作者：
de Paz, JL;Noti, C;Seeberger, PH
我们提出了第一个含有合成肝素寡糖的微阵列的制备，以阐明各种生物过程中所涉及的肝素-蛋白质相互作用。为此，我们已经开发了一种新的接头策略，该策略与高度硫酸化寡糖合成所需的保护基团操作相容，并且还可以扩展到自动化固相方法。正交保护的胺接头的策略性放置是阵列构建成功的关键。这些肝素芯片允许通过使用3皮摩尔的蛋白质高通量筛选寡糖。通过探测两种肝素结合生长因子FGF-1和FGF-2的碳水化合物亲和力，证明了新方法的潜力，这两种生长因子与几种肿瘤的发展和分化有关。
We present the first preparation of microarrays containing synthetic heparin oligosaccharides in order to elucidate the heparin−protein interactions involved in a variety of biological processes. For this purpose, we have developed a novel linker strategy that is compatible with the protecting-group manipulations required for the synthesis of the highly sulfated oligosaccharides and can also be extended to an automated solid phase approach. Strategic placement of the orthogonally protected amine linker was key to the success of the array construction. These heparin chips allow for the high-throughput screening of oligosaccharides by using ∼picomoles of protein. The potential of the new method was demonstrated by probing the carbohydrate affinity of two heparin-binding growth factors, FGF-1 and FGF-2, that are implicated in the development and differentiation of several tumors.