Synthesis of a Pentasaccharide and Neoglycoconjugates Related to Fungal α-(1→3)-Glucan and Their Use in the Generation of Antibodies to Trace Aspergillus fumigatus Cell Wall
Synthesis of a Pentasaccharide and Neoglycoconjugates Related to Fungal α-(1→3)-Glucan and Their Use in the Generation of Antibodies to Trace Aspergillus fumigatus Cell Wall
复制标题
DOI：
10.1002/chem.201404770
复制
发表时间：
2015-01-12
影响因子：
4.3
通讯作者：
Nifantiev, Nikolay E.
中科院分区：
文献类型：
--
作者：
Komarova, Bozhena S.;Orekhova, Maria V.;Nifantiev, Nikolay E.
3-氨丙基-（13）-五葡糖苷是烟曲霉细胞壁中的-（13）-葡聚糖的一个片段。具有立体定向的6-O-苯甲酰基的单糖和二糖N-苯基三氟乙酰亚胺酯的应用对于立体选择性-葡糖基化是必不可少的。在产物中，对甲氧基苯基和乙酰丙酸酰基分别作为异头位置和3-OH基团的正交保护基。将它们从共享块中移除导致用于合成五糖的供体和受体。游离-（13）-五糖苷与生物素和牛血清白蛋白（BSA）的偶联为真菌学研究提供了糖缀合物工具。用BSA结合物免疫小鼠，诱导产生识别A.烟曲霉细胞壁的形态特征及形态类型的鉴别。这一发现代表了开发诊断测试系统和疫苗以检测和对抗这种威胁生命的病原体的第一步。
3-Aminopropyl -(13)-pentaglucoside, a fragment of -(13)-glucan of the cell wall of Aspergillus fumigatus, has been synthesized in a blockwise approach. The application of mono- and disaccharide N-phenyltrifluoroacetimidates bearing a stereodirecting 6-O-benzoyl group was essential for stereoselective -glucosylations. In the products, p-methoxyphenyl and levulinoyl groups served as orthogonal protecting groups for the anomeric position and 3-OH group, respectively. Their removal from shared blocks led to donors and acceptors that were used for the synthesis of pentasaccharides. Coupling of free -(13)-pentaglucoside with biotin and bovine serum albumin (BSA) gave glycoconjugate tools for mycological studies. Immunization of mice with the BSA conjugate induced the generation of antibodies that recognize -(13)-glucan on A. fumigatus cell wall and distinguish its morphotypes. This discovery represents a first step to the development of a diagnostic test system and a vaccine to detect and fight this life-threatening pathogen.