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用于快速鉴定高亲和力唾液酸结合免疫球蛋白样凝集素配体的唾液酸苷类似物阵列

Sialoside analogue arrays for rapid identification of high affinity siglec ligands.

作者信息

Blixt Ola, Han Shoufa, Liao Liang, Zeng Ying, Hoffmann Julia, Futakawa Satoshi, Paulson James C

机构信息

Departments of Chemical Physiology and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

出版信息

J Am Chem Soc. 2008 May 28;130(21):6680-1. doi: 10.1021/ja801052g. Epub 2008 May 2.

Abstract

The siglec family of sialic acid binding proteins participates in diverse cell surface biology that includes regulation of immune cell signaling and the interaction of neuronal cells with glial cells. The weak intrinsic affinity of the natural sialoside ligands has hampered the development of synthetic ligand based probes needed to elucidate their roles in siglec function. In this report, we describe a glycan microarray comprising a library of 9-acyl-substituted sialic acids incorporated into sialosides containing the Neu5Acalpha2-3Gal and Neu5Acalpha-6Gal linkages commonly recognized by the siglecs. The array is demonstrated to exhibit utility for detecting 9-acyl substituents that increase the affinity of siglecs for their ligands. Substituents that increase affinity are anticipated to be useful for the design of high affinity ligand based probes of siglec function.

摘要

唾液酸结合蛋白的唾液酸结合免疫球蛋白样凝集素(Siglec)家族参与多种细胞表面生物学过程,包括免疫细胞信号传导的调节以及神经元细胞与神经胶质细胞的相互作用。天然唾液酸苷配体的内在亲和力较弱,这阻碍了用于阐明其在Siglec功能中作用的基于合成配体的探针的开发。在本报告中,我们描述了一种聚糖微阵列,该阵列包含一个9-酰基取代唾液酸文库,这些唾液酸被掺入含有Siglec通常识别的Neu5α2-3Gal和Neu5α-6Gal连接的唾液酸苷中。该阵列被证明可用于检测增加Siglec对其配体亲和力的9-酰基取代基。预计增加亲和力的取代基将有助于设计基于高亲和力配体的Siglec功能探针。

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