Chemical tools to study eukaryotic protein glycosylation

糖共轭化合物是生物体内的关键生物分子结构，由几个不同的相互连接的糖单元组成，最常见的是附着在脂质或蛋白质上。人类基因组中大约300个基因被分配给糖结合物的正确的逐步组装和拆解，这突显了不同的糖结合物所发挥的重要作用。这种受调控的糖结合物结构多样性的目的在于它们能够调节蛋白质的功能，调节分子相互作用，以及改变蛋白质的物理性质和稳定性。过去几年的一系列惊人发现表明，蛋白质糖基化直接调节细胞内和细胞间的信号和转录。值得注意的是，尽管糖生物学作为一个突出和活跃的研究领域不断增长，但与其他领域相比，这一领域的研究人员可用的工具要有限得多。为了解决这一差距，我们在这个项目中专注于开发化学工具来帮助研究三种较少研究的糖基化形式。虽然我们感兴趣的糖偶联物已经知道20多年了，但在阐明它们在生物学中的功能作用方面进展有限。这种有限的进展在很大程度上是由于缺乏分子和化学工具来探索这些多糖结构和处理它们的酶的作用。因此，这里描述的短期研究计划包括开发一些研究工具，以便于破译这些形式的O-糖基化的分子作用，并评估负责处理这些多糖的酶的活性。我们研究小组的长期目标是为糖科学界提供有用的工具，从而增加对不同形式糖基化功能重要性的理解。

Glycoconjugates are key biomolecular structures within organisms that are composed of several different interlinked sugar units, most commonly attached to either lipids or proteins. The allocation of approximately 300 genes within the human genome to the proper stepwise assembly and disassembly of glycoconjugates highlights the important roles played by diverse glycoconjugates. The purpose of this regulated structural diversity of glycoconjugates lies in their ability to modulate protein function, mediate molecular interactions, as well as to alter the physical properties and stability of proteins. A striking series of findings in the past few years have suggested that protein glycosylation acts directly to regulates intra- and intercellular signaling and transcription. Remarkably, despite the continuing growth of glycobiology as a prominent and active field of research, the tools available to researchers in this area as compared to other fields are far more limited. To address this gap, we focus in this program on developing chemical tools to aid study of three less investigated forms of glycosylation. Although the glycoconjugates we are interested in have been known for over 20 years, there has been limited progress in elucidating their functional roles in biology. This limited progress stems, in large part, from the lack of molecular and chemical tools available for probing the roles of these glycan structures and the enzymes that process them. Accordingly, the short term program of research described here involves the development of a number of research tools to facilitate decoding the molecular role of these forms of O-glycosylation and to evaluate the activities of the enzymes responsible for processing these glycans. The long term aim of our research group is to provide the glycoscience community with useful tools and thus increase understanding of the functional importance of different forms of glycosylation.