Presentation, presentation, presentation! Molecular-level insight into linker effects on glycan array screening data
Presentation, presentation, presentation! Molecular-level insight into linker effects on glycan array screening data
复制标题
DOI：
10.1093/glycob/cwt083
复制
发表时间：
2014-01-01
期刊：
影响因子：
4.3
通讯作者：
Woods, Robert J.
中科院分区：
文献类型：
--
作者：
Grant, Oliver C.;Smith, Hannah M. K.;Woods, Robert J.
细胞表面聚糖模式的变化是许多不同疾病和癌症类型存在的标志，为诊断和治疗中的聚糖靶向试剂和治疗提供了相对未开发的利基。对于任何聚糖靶向试剂的成功来说，最重要的是能够在人体中存在的大量不同聚糖中特异性识别靶标。确定特异性的最佳技术是聚糖阵列筛选，其中聚糖结合蛋白（GBP）可以同时针对多种聚糖进行筛选。聚糖阵列筛选为GBP特异性提供了无与伦比的洞察力，但数据解释在识别由改变的聚糖呈递引起的假阴性结合方面存在困难，与用于将聚糖缀合至表面的接头相关。在这项工作中，我们模拟的结构和动力学的连接器中采用的聚糖阵列的功能性糖组学协会。建模考虑了阵列的物理存在和表面极性，并提供了一个基于结构的合理化的假阴性结果所产生的所谓的“链接器效应”。“这些结果也可以作为在生物学背景下解释聚糖阵列筛选数据的指导;特别是，我们表明，尝试使用天然氨基酸作为接头可能容易出现意想不到的影响聚糖识别的伪影。
Changes in cell-surface glycan patterns are markers of the presence of many different disease and cancer types, offering a relatively untapped niche for glycan-targeting reagents and therapeutics in diagnosis and treatment. Of paramount importance for the success of any glycan-targeting reagent is the ability to specifically recognize the target among the plethora of different glycans that exist in the human body. The preeminent technique for defining specificity is glycan array screening, in which a glycan-binding protein (GBP) can be simultaneously screened against multiple glycans. Glycan array screening has provided unparalleled insight into GBP specificity, but data interpretation suffers from difficulties in identifying false-negative binding arising from altered glycan presentation, associated with the linker used to conjugate the glycan to the surface. In this work, we model the structure and dynamics of the linkers employed in the glycan arrays developed by the Consortium for Functional Glycomics. The modeling takes into account the physical presence and surface polarity of the array, and provides a structure-based rationalization of false-negative results arising from the so-called "linker effect." The results also serve as a guide for interpreting glycan array screening data in a biological context; in particular, we show that attempts to employ natural amino acids as linkers may be prone to unexpected artifacts compromising glycan recognition.