Ma Zuchao, Ensley Harry E, Lowman Douglas W, Kruppa Michael D, Williams David L
Department of Surgery, Quillen College of Medicine, East Tennessee State University, Johnson City, TN37614, USA; Drug Discovery and Synthesis Core, Quillen College of Medicine, East Tennessee State University, Johnson City, TN37614, USA; Center for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN37614, USA.
Department of Surgery, Quillen College of Medicine, East Tennessee State University, Johnson City, TN37614, USA; Drug Discovery and Synthesis Core, Quillen College of Medicine, East Tennessee State University, Johnson City, TN37614, USA; Center for Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN37614, USA.
Carbohydr Res. 2025 Jan;547:109325. doi: 10.1016/j.carres.2024.109325. Epub 2024 Nov 22.
Fungal mannans are located on the exterior of the fungal cell wall, where they interact with the environment and, ultimately, the human host. Mannans play a major role in shaping the innate immune response to fungal pathogens. Understanding the phosphodiester linkage and mannosyl repeat units in the acid-labile portion of mannans is crucial for comprehending their structure/activity relationships and for development of anti-fungal vaccines and immunomodulators. The phosphodiester linkages connect the acid-stable and acid-labile portions of the mannan polymer. Phosphate groups are attached to positions 4 and/or 6 of mannosyl repeat units in the acid-stable portion and to position 1 of mannosyl repeat units in the acid-labile portion. This review focuses on the synthesis of phosphodiester linkages as an approach to the development of mannan glycomimetics, which are based on natural product fungal mannans. Development of successful synthetic strategies for the phosphodiester linkages may enable the production of mannan glycomimetics that elicit anti-fungal immune responses against existing and emerging fungal pathogens, such as Candida albicans and Candida auris.
真菌甘露聚糖位于真菌细胞壁的外部，在那里它们与环境以及最终与人类宿主相互作用。甘露聚糖在塑造针对真菌病原体的固有免疫反应中起主要作用。了解甘露聚糖酸不稳定部分中的磷酸二酯键和甘露糖基重复单元对于理解它们的结构/活性关系以及开发抗真菌疫苗和免疫调节剂至关重要。磷酸二酯键连接甘露聚糖聚合物的酸稳定部分和酸不稳定部分。磷酸基团连接到酸稳定部分中甘露糖基重复单元的4位和/或6位以及酸不稳定部分中甘露糖基重复单元的1位。本综述重点关注磷酸二酯键的合成，以此作为开发基于天然产物真菌甘露聚糖的甘露聚糖糖模拟物的一种方法。成功的磷酸二酯键合成策略的开发可能使生产出能引发针对现有和新出现的真菌病原体（如白色念珠菌和耳念珠菌）的抗真菌免疫反应的甘露聚糖糖模拟物成为可能。
