Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York, USA.
Nat Chem Biol. 2011 Oct 9;7(11):827-33. doi: 10.1038/nchembio.673.
Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven, Golgi-synthesized glycosaminoglycans are not believed to have predictable or deterministic sequences. Bikunin peptidoglycosaminoglycans were prepared and fractionated to obtain a collection of size-similar and charge-similar chains. Fourier transform mass spectral analysis identified a small number of parent molecular ions corresponding to monocompositional peptidoglycosaminoglycans. Fragmentation using collision-induced dissociation unexpectedly afforded a single sequence for each monocompositional parent ion, unequivocally demonstrating the presence of a defined sequence. The biosynthetic pathway common to all proteoglycans suggests that even more structurally complex proteoglycans, such as heparan sulfate, may have defined sequences, requiring a readjustment in the understanding of information storage in complex glycans.
蛋白聚糖是调节所有高等生物关键生物途径的复杂糖缀合物。 双 Kunin 是最简单的蛋白聚糖,带有一条单一的糖胺聚糖链,是一种用于治疗急性胰腺炎的丝氨酸蛋白酶抑制剂。 与受模板驱动的核酸和蛋白质不同,高尔基合成的糖胺聚糖据信没有可预测或确定的序列。 制备和分级分离 Bikunin 糖肽聚糖,以获得一系列大小相似和电荷相似的链。 傅里叶变换质谱分析鉴定出少量对应于单组成糖肽聚糖的母体分子离子。 使用碰撞诱导解离进行碎片化出乎意料地为每个单组成母离子提供了单一序列,明确证明了存在确定的序列。 所有蛋白聚糖共有的生物合成途径表明,即使是结构更复杂的蛋白聚糖,如肝素硫酸盐,也可能具有确定的序列,这需要重新调整对复杂聚糖中信息存储的理解。