当前位置: X-MOL 学术Nat. Chem. › 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.)
Rapid phenolic O -glycosylation of small molecules and complex unprotected peptides in aqueous solvent
Nature Chemistry ( IF 19.2 ) Pub Date : 2018-04-30 , DOI: 10.1038/s41557-018-0041-8
Tyler J Wadzinski 1 , Angela Steinauer 1 , Liana Hie 1 , Guillaume Pelletier 1 , Alanna Schepartz 1 , Scott J Miller 1
Affiliation  

Glycosylated natural products and synthetic glycopeptides represent a significant and growing source of biochemical probes and therapeutic agents. However, methods that enable the aqueous glycosylation of endogenous amino acid functionality in peptides without the use of protecting groups are scarce. Here, we report a transformation that facilitates the efficient aqueous O-glycosylation of phenolic functionality in a wide range of small molecules, unprotected tyrosine, and tyrosine residues embedded within a range of complex, fully unprotected peptides. The transformation, which uses glycosyl fluoride donors and is promoted by Ca(OH)2, proceeds rapidly at room temperature in water, with good yields and selective formation of unique anomeric products depending on the stereochemistry of the glycosyl donor. High functional group tolerance is observed, and the phenol glycosylation occurs selectively in the presence of virtually all side chains of the proteinogenic amino acids with the singular exception of Cys. This method offers a highly selective, efficient, and operationally simple approach for the protecting-group-free synthesis of O-aryl glycosides and Tyr-O-glycosylated peptides in water.



中文翻译:


小分子和复杂的未保护肽在水性溶剂中的快速酚 O -糖基化



糖基化天然产物和合成糖肽是生化探针和治疗剂的重要且不断增长的来源。然而,能够在不使用保护基的情况下对肽中的内源氨基酸功能性进行水性糖基化的方法很少。在这里,我们报告了一种转化,该转化促进了各种小分子、未受保护的酪氨酸和嵌入一系列复杂的、完全未受保护的肽中的酪氨酸残基中酚官能团的有效水性O-糖基化。该转化使用糖基氟供体并由 Ca(OH) 2促进,在室温下在水中快速进行,具有良好的产率,并根据糖基供体的立体化学选择性形成独特的异头产物。观察到高官能团耐受性,并且在蛋白质氨基酸的几乎所有侧链存在的情况下选择性地发生苯酚糖基化(半胱氨酸除外)。该方法为在水中无保护基合成O-芳基糖苷和 Tyr- O-糖基化肽提供了一种高选择性、高效且操作简单的方法。

更新日期:2018-05-01
down
wechat
bug