在微孔板中合成糖阵列。

Synthesis of sugar arrays in microtiter plate.

作者信息

Fazio Fabio, Bryan Marian C, Blixt Ola, Paulson James C, Wong Chi-Huey

机构信息

Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

出版信息

J Am Chem Soc. 2002 Dec 4;124(48):14397-402. doi: 10.1021/ja020887u.

DOI:10.1021/ja020887u

PMID:12452714

Abstract

1,3-Dipolar cycloadditions between azides and alkynes were exploited to attach oligosaccharides to a C(14) hydrocarbon chain that noncovalently binds to the microtiter well surface. Synthesis of sugar arrays was performed on a micromolar scale in situ in the microtiter plate. As a model study, the beta-galactosyllipid 5 was displayed on a 4-micromol scale. Formation of product was confirmed via ESI-MS, and the yield was determined via chemical and biological assays. Several complex carbohydrates (6-16) were also displayed in microtiter plates and successfully screened with various lectins. Moreover, sialyl Lewis x (17) was synthesized via the enzymatic fucosylation of a precursor displayed in the plate. Studies on inhibition of this biotransformation have been carried out, and the IC(50) value found for the known inhibitor 20 was consistent with previous studies in solution.

摘要

利用叠氮化物与炔烃之间的1,3-偶极环加成反应，将寡糖连接到与微量滴定孔表面非共价结合的C(14)烃链上。糖阵列的合成在微量滴定板中原位以微摩尔规模进行。作为模型研究，β-半乳糖脂5以4微摩尔规模展示。通过电喷雾电离质谱法（ESI-MS）确认产物的形成，并通过化学和生物学测定法确定产率。几种复合碳水化合物（6-16）也展示在微量滴定板中，并用各种凝集素成功进行了筛选。此外，通过对板中展示的前体进行酶促岩藻糖基化反应合成了唾液酸化路易斯x（17）。已经开展了对这种生物转化抑制作用的研究，已知抑制剂20的半数抑制浓度（IC(50)）值与先前在溶液中的研究结果一致。