Rios Pablo, Carter Tom S, Mooibroek Tiddo J, Crump Matthew P, Lisbjerg Micke, Pittelkow Michael, Supekar Nitin T, Boons Geert-Jan, Davis Anthony P
School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen Ø, Denmark.
Angew Chem Int Ed Engl. 2016 Mar 1;55(10):3387-92. doi: 10.1002/anie.201510611. Epub 2016 Jan 28.
The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc-β-OMe with Ka ≈20,000 m(-1), whereas the other one binds an O-GlcNAcylated peptide with Ka ≈70,000 m(-1). These values substantially exceed those usually measured for GlcNAc-binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl-peptide complex can be explained by extra-cavity interactions, raising the possibility of a family of complementary receptors for O-GlcNAc in different contexts.
含有间苯二甲酰间隔基的芘基四胺组合已产生了两种新型水溶性碳水化合物受体（“合成凝集素”）。这两种体系在水溶液中对N-乙酰葡糖胺（GlcNAc）衍生物均表现出出色的亲和力。一种受体与甲基糖苷GlcNAc-β-OMe结合，其Ka≈20,000 m⁻¹，而另一种受体与O-GlcNAc化肽结合，其Ka≈70,000 m⁻¹。这些值大大超过了通常测定的GlcNAc结合凝集素的值。在核磁共振时间尺度上的缓慢交换使得能够对几种复合物进行结构测定。正如预期的那样，碳水化合物单元夹在芘之间，烷氧基和NHAc基团出现在侧面。GlcNAc基肽复合物的高亲和力可以通过腔外相互作用来解释，这增加了在不同情况下存在一系列O-GlcNAc互补受体的可能性。
