Generation of glucosylated sn-1-glycerolphosphate teichoic acids: glycerol stereochemistry affects synthesis and antibody interaction,RSC Chemical Biology

当前位置： X-MOL 学术 › RSC Chem. Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Generation of glucosylated sn-1-glycerolphosphate teichoic acids: glycerol stereochemistry affects synthesis and antibody interaction
RSC Chemical Biology ( IF 4.2 ) Pub Date : 2020-12-23 , DOI: 10.1039/d0cb00206b
Francesca Berni ₁ , Liming Wang ₁ , Ermioni Kalfopoulou ₂ , D Linh Nguyen ₃ , Daan van der Es ₁ , Johannes Huebner ₂ , Herman S Overkleeft ₁ , Cornelis H Hokke ₃ , Gijsbert A van der Marel ₁ , Angela van Diepen ₃ , Jeroen D C Codée ₁

Affiliation

Lipoteichoic acids (LTAs) have been addressed as possible antigen candidates for vaccine development against several opportunistic Gram-positive pathogens. The study of structure-immunogenicity relationship represents a challenge due to the heterogenicity of LTA extracted from native sources. LTAs are built up from glycerol phosphate (GroP) repeating units and they can be substituted at the C-2-OH with carbohydrate appendages or D-alanine residues. The substitution pattern, but also the absolute chirality of the GroP residues can impact the interaction with chiral biomolecules including antibodies and biosynthesis enzymes. We have generated a set of diastereomeric GroP hexamers bearing a glucosyl modification at one of the residues. The chirality of the glycerol building block had an important impact on the stereoselectivity of the glycosylation reaction between the glycosyl donor and the glycerol C-2-OH acceptor. The GroP C-2-chirality also played an important role in the interaction with TA recognizing antibodies. These findings have important implications for the design and synthesis of synthetic TA fragments for diagnostic and therapeutic applications.

中文翻译：

葡萄糖基化 sn-1-甘油磷酸磷壁酸的生成：甘油立体化学影响合成和抗体相互作用

脂磷壁酸 (LTA) 已被认为是针对几种机会性革兰氏阳性病原体的疫苗开发的可能候选抗原。由于从天然来源提取的 LTA 具有异质性，结构与免疫原性关系的研究面临着挑战。LTA 由磷酸甘油 (GroP) 重复单元组成，它们的 C-2-OH 可以被碳水化合物附加物或D-丙氨酸残基取代。GroP 残基的取代模式以及绝对手性都会影响与手性生物分子（包括抗体和生物合成酶）的相互作用。我们生成了一组非对映体 GroP 六聚体，其中一个残基带有葡萄糖基修饰。甘油结构单元的手性对糖基供体和甘油 C-2-OH 受体之间糖基化反应的立体选择性具有重要影响。GroP C-2-手性在与 TA 识别抗体的相互作用中也发挥着重要作用。这些发现对于用于诊断和治疗应用的合成 TA 片段的设计和合成具有重要意义。

更新日期：2020-12-23

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文