Boronic acid functionalized peptidyl synthetic lectins: combinatorial library design, peptide sequencing, and selective glycoprotein recognition.

Boronic acid functionalized peptidyl synthetic lectins: combinatorial library design, peptide sequencing, and selective glycoprotein recognition.
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硼酸官能化肽基合成凝集素:组合库设计,肽测序和选择性糖蛋白识别。

DOI:
10.1021/co100054e
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发表时间:
2011-05-09
影响因子:
--
通讯作者:
Thompson, Paul R.
Thompson, Paul R.
中科院分区:
化学3区
文献类型:
--
作者:
Bicker, Kevin L.;Sun, Jing;Lavigne, John J.;Thompson, Paul R.

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细胞膜和分泌的糖蛋白的异常糖基化是包括癌症在内的各种疾病状态的标志。目前用于识别这些糖蛋白的天然凝集素价格昂贵,难以生产,并且对严格使用不稳定。在此,我们描述了几个硼酸功能化的肽为基础的合成凝集素(SL)库的设计和合成,以及优化的方法来获得这些SL的肽序列。SL文库随后用于鉴定对各种糖蛋白具有高达5倍选择性的SL。SL将不可避免地在癌症诊断中发挥作用,因为它们不存在天然凝集素的缺点,并且这些库的组合性质允许识别几乎任何糖基化生物分子的SL。
Aberrant glycosylation of cell membrane and secreted glycoproteins is a hallmark of various disease states, including cancer. The natural lectins currently used in the recognition of these glycoproteins are costly, difficult to produce, and unstable towards rigorous use. Herein we describe the design and synthesis of several boronic acid functionalized peptide-based synthetic lectin (SL) libraries, as well as the optimized methodology for obtaining peptide sequences of these SLs. SL libraries were subsequently used to identify SLs with as high as 5-fold selectivity for various glycoproteins. SLs will inevitably find a role in cancer diagnositics, given that they do not suffer from the drawbacks of natural lectins and that the combinatorial nature of these libraries allows for the identification of an SL for nearly any glycosylated biomolecule.
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