Pett Christian, Westerlind Ulrika
Gesellschaft zur Förderung der Analytischen Wissenschaften e.V. ISAS, Leibniz Institute for Analytical Sciences, Otto-Hahn-Str. 6b, 44227 Dortmund (Germany).
Chemistry. 2014 Jun 10;20(24):7287-99. doi: 10.1002/chem.201400162. Epub 2014 May 19.
Mucins are a class of highly O-glycosylated proteins found on the surface of cells in epithelial tissues. O-Glycosylation is crucial for the functionality of mucins and changes therein can have severe consequences for an organism. With that in mind, the elucidation of interactions of carbohydrate binding proteins with mucins, whether in morbidly altered or unaltered conditions, continue to shed light on mechanisms involved in diseases like chronic inflammations and cancer. Despite the known importance of type-1 and type-2 elongated mucin cores 1-4 in glycobiology, the corresponding type-1 structures are much less well studied. Here, the first chemical synthesis of extended mucin type-1 O-glycan core 1-3 amino acid structures based on a convergent approach is presented. By utilizing differentiation in acceptor reactivity, shared early stage Tn- and T-acceptor intermediates were elongated with a common type-1 [β-D-Gal-1,3-β-D-GlcNAc] disaccharide, which allows for straightforward preparation of diverse glycosylated amino acids carrying the type-1 mucin core 1-3 saccharides. The obtained glycosylated 9-fluorenylmethoxycarbonyl (Fmoc)-protected amino acid building blocks were employed in synthesis of type-1 mucin glycopeptides, which are useful in biological applications.
黏蛋白是一类高度O-糖基化的蛋白质，存在于上皮组织细胞表面。O-糖基化对于黏蛋白的功能至关重要，其变化可能对生物体产生严重后果。鉴于此，阐明碳水化合物结合蛋白与黏蛋白之间的相互作用，无论处于病态改变还是未改变的状态，都能继续揭示慢性炎症和癌症等疾病所涉及的机制。尽管1型和2型延伸黏蛋白核心1-4在糖生物学中的重要性已为人所知，但相应的1型结构的研究却少得多。在此，我们展示了基于收敛方法首次化学合成延伸的黏蛋白1型O-聚糖核心1-3氨基酸结构。通过利用受体反应性的差异，共同的早期Tn-和T-受体中间体用共同的1型[β-D-半乳糖-1,3-β-D-乙酰氨基葡萄糖]二糖进行延伸，这使得直接制备携带1型黏蛋白核心1-3糖类的各种糖基化氨基酸成为可能。所获得的糖基化9-芴甲氧羰基（Fmoc）保护的氨基酸构建块被用于合成1型黏蛋白糖肽，其在生物学应用中很有用。
