芳基聚焦物的合成及其对DC-SIGN受体结合亲和力的评价。

IF 2.7 3区化学 Q1 CHEMISTRY, ORGANIC

Organic & Biomolecular Chemistry Pub Date : 2025-04-11 DOI:10.1039/d5ob00472a

Rohit Chavan, Maurice Besch, Jonathan Lefèbre, Christoph Rademacher, Petra Ménová

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引用次数: 0

摘要

DC-SIGN是一种在抗原提呈细胞上表达的c型凝集素受体，对病原体识别和免疫调节至关重要。虽然大多数拟糖DC-SIGN配体是基于甘露糖的，但基于聚焦的配体具有更高的选择性，可能会减少脱靶效应。本研究报道了芳基α-L-聚焦物的立体选择性合成及其对DC-SIGN的结合亲和力。通过1H-15N HSQC NMR和竞争分析，我们确定了3-三氟甲基苯基α-L- focuside为最佳配体，其KD和IC50值均在三位数的微摩尔范围内，并且不仅与标准位点结合，而且与二级变结构位点结合。

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Aryl fucosides: synthesis and evaluation of their binding affinity towards the DC-SIGN receptor.

DC-SIGN, a C-type lectin receptor expressed on antigen presenting cells, is crucial for pathogen recognition and immune modulation. While most glycomimetic DC-SIGN ligands are mannose-based, fucose-based ligands offer enhanced selectivity, potentially reducing off-target effects. This study reports the stereoselective synthesis of aryl α-L-fucosides and their binding affinity for DC-SIGN. Using ¹H-¹⁵N HSQC NMR and a competition assay, we identified 3-trifluoromethylphenyl α-L-fucoside as the best ligand, exhibiting both K_D and IC₅₀ values in a three-digit micromolar range and binding not only to the canonical site, but also to a secondary allosteric site.

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来源期刊

Organic & Biomolecular Chemistry 化学-有机化学

CiteScore

5.50

自引率

9.40%

发文量

1056

审稿时长

1.3 months

期刊介绍： Organic & Biomolecular Chemistry is an international journal using integrated research in chemistry-organic chemistry. Founded in 2003 by the Royal Society of Chemistry, the journal is published in Semimonthly issues and has been indexed by SCIE, a leading international database. The journal focuses on the key research and cutting-edge progress in the field of chemistry-organic chemistry, publishes and reports the research results in this field in a timely manner, and is committed to becoming a window and platform for rapid academic exchanges among peers in this field. The journal's impact factor in 2023 is 2.9, and its CiteScore is 5.5.