在溶液和固体阶段的O-曼诺基的化学酶合成
Robert Šardzík1, Anthony P Green, Nicolas Laurent
1School of Chemistry, Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester M1 7DN, UK.
Journal of the American Chemical Society
|March 1, 2012
概括
研究人员合成了复杂的O-mannosyl glycans,对α-dystroglycan (α-DG) 功能至关重要. 这一突破使得通过提供纯糖样本,可以进一步研究先天性肌肉发育不良.
科学领域:
- 碳水化合物化学 碳水化合物化学
- 葡萄糖生物学 葡萄糖生物学
- 分子生物学分子生物学
背景情况:
- O-曼诺西尔甘氨酸调节了α-DG (α-DG) 的功能.
- 缺陷的α-DG糖化与先天性肌肉发育不良有关.
- 了解这些甘氨酸的精确分子作用需要纯净,均的样本.
研究的目的:
- 开发用于生产纯O-曼诺西尔糖的合成方法.
- 合成在α-DG上发现的最丰富的O-曼诺西尔糖.
- 为进一步对α-DG功能进行生物学研究提供工具.
主要方法:
- 通过生物模拟步骤组装对糖的总合成.
- 开发一种单酶级联,用于快速的四糖合成.
- 在金色微阵列平台上合成糖的固体相合成.
主要成果:
- 含有丰富的α-DG O-曼诺西尔四糖NeuNAcα2-3Galβ1-4GlcNAcβ1-2Manα的糖的第一个总合成.
- 获取自然存在的单糖,二糖和三糖基结构.
- 快速酶合成和固相微阵列合成的演示.
结论:
- 开发的合成策略为研究O-曼诺西尔甘氨酸和α-DG提供了必要的工具.
- 这些方法将有助于研究先天性肌肉衰竭的分子机制.
- 合成的糖将有助于理解O-曼诺西尔糖化酶的生物学意义.
相关概念视频
Peptidoglycan Synthesis
Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan biosynthesis begins in...
ATP and Macromolecule Synthesis
Biological macromolecules are organic compounds, predominantly composed of carbon atoms. The carbon atoms are covalently bonded with hydrogen, oxygen, nitrogen, and other minor elements. There are four major biological macromolecule classes: carbohydrates, lipids, proteins, and nucleic acids.
Most macromolecules are composed of single subunits, or building blocks, called monomers. The monomers combine with each other using covalent bonds to form larger molecules known as polymers.
Conversion of...
Most macromolecules are composed of single subunits, or building blocks, called monomers. The monomers combine with each other using covalent bonds to form larger molecules known as polymers.
Conversion of...
Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
Production of Pharmaceuticals
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...


