Chemoenzymatic Synthesis of N-glycan Positional Isomers and Evidence for Branch Selective Binding by Monoclonal Antibodies and Human C-type Lectin Receptors,ACS Chemical Biology

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Chemoenzymatic Synthesis of N-glycan Positional Isomers and Evidence for Branch Selective Binding by Monoclonal Antibodies and Human C-type Lectin Receptors
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2018-06-12 00:00:00 , DOI: 10.1021/acschembio.8b00431
Begoña Echeverria ₁ , Sonia Serna ₁ , Silvia Achilli ₂ , Corinne Vivès ₂ , Julie Pham ₁ , Michel Thépaut ₂ , Cornelis H. Hokke ₃ , Franck Fieschi ₂ , Niels-Christian Reichardt _{1,

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Affiliation

Here, we describe a strategy for the rapid preparation of pure positional isomers of complex N-glycans to complement an existing array comprising a larger number of N-glycans and smaller glycan structures. The expanded array was then employed to study context-dependent binding of structural glycan fragments by monoclonal antibodies and C-type lectins. A partial enzymatic elongation of semiprotected core structures was combined with the protecting-group-aided separation of positional isomers by preparative HPLC. This methodology, which avoids the laborious chemical differentiation of antennae, was employed for the preparation of eight biantennary N-glycans with Galβ1,4GlcNAc (LN), GalNAcβ1,4GlcNAc (LDN), and GalNAcβ1,4[Fucα1,3]GlcNAc (LDNF) motifs presented on either one or both antennae. Screening of the binding specificities of three anti-Le^X monoclonal IgM antibodies raised against S. mansoni glycans and three C-type lectin receptors of the innate immune system, namely DC-SIGN, DC-SIGNR, and LSECtin, revealed a surprising context-dependent fine specificity for the recognition of the glycan motifs. Moreover, we observed a striking selection of one individual positional isomer over the other by the C-type lectins tested, underscoring the biological relevance of the structural context of glycan elements in molecular recognition.

中文翻译：

化学酶法合成的N-聚糖位置异构体和单克隆抗体和人类C型凝集素受体的分支选择性结合的证据。

在这里，我们描述了一种快速制备复杂N-聚糖的纯位置异构体的策略，以补充包含大量N-聚糖和较小聚糖结构的现有阵列。然后将扩展的阵列用于研究单克隆抗体和C型凝集素对结构聚糖片段的背景依赖性结合。通过制备型HPLC将半保护核心结构的部分酶促延伸与位置异构体的保护基辅助分离相结合。该方法避免了繁琐的触角化学区分，被用于制备八种带有Galβ1,4GlcNAc（LN），GalNAcβ1,4GlcNAc（LDN）和GalNAcβ1,4[Fucα1,3] GlcNAc（LDNF）的双触角N-聚糖。）出现在一个或两个触角上的图案。三种抗Le抗体结合特异性的筛选针对曼氏沙门氏菌聚糖和先天免疫系统的三个C型凝集素受体（即DC-SIGN，DC-SIGNR和LSECtin）产生的^X单克隆IgM抗体显示出令人惊讶的上下文相关的精细特异性，可识别聚糖基序。此外，我们观察到，通过测试的C型凝集素，一个单独的位置异构体比其他一个位置异构体引人注目，这突出了分子识别中聚糖元素结构背景的生物学相关性。

更新日期：2018-06-12

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