Rediscovery of 4‐Trehalosamine as a Biologically Stable, Mass‐Producible, and Chemically Modifiable Trehalose Analog
Rediscovery of 4‐Trehalosamine as a Biologically Stable, Mass‐Producible, and Chemically Modifiable Trehalose Analog
复制标题
DOI：
10.1002/adbi.202101309
复制
发表时间：
2022-03
期刊：
影响因子：
3.7
通讯作者：
S. Wada;Honami Arimura;Miho Nagayoshi;R. Sawa;Y. Kubota;K. Matoba;C. Hayashi;Y. Shibuya;Masaki Hatano;Yasuhiro Takehana;Shun‐ichi Ohba;Y. Kobayashi;Takumi Watanabe;M. Shibasaki;M. Igarashi
中科院分区：
文献类型：
--
作者：
S. Wada;Honami Arimura;Miho Nagayoshi;R. Sawa;Y. Kubota;K. Matoba;C. Hayashi;Y. Shibuya;Masaki Hatano;Yasuhiro Takehana;Shun‐ichi Ohba;Y. Kobayashi;Takumi Watanabe;M. Shibasaki;M. Igarashi
非还原性二糖海藻糖在各种产品中用作稳定剂和保湿剂，是一种潜在的药用药物，对各种疾病的动物模型显示出疗效。然而，它的使用受到限制，因为它被海藻糖酶水解，海藻糖酶是一种在多种生物中广泛表达的酶。制备了几种海藻糖类似物，包括微生物代谢产物4-海藻糖胺，并证实了它们的高生物稳定性。为了进一步分析，选择4-海藻糖胺，因为其显示高产量。与海藻糖相比，4-海藻糖胺具有更好或相当的保护活性和中性pH附近的高缓冲能力。4-海藻糖胺的另一个优点是其化学可修饰性：简单的反应产生其各种衍生物。标记的探针和洗涤剂在一锅反应中合成，以验证其生产的可行性，并确认其各自应用的实用性。标记的探针用于分枝杆菌染色。虽然衍生物去污剂可以有效地用于膜蛋白研究，但长链去污剂在培养细胞中显示出比海藻糖强1000-3000倍的自噬诱导活性，有望成为药物先导和研究试剂。这些结果表明，4-海藻糖胺是用于各种目的的有用的海藻糖替代品，也是生产新的有用衍生物的材料。
Nonreducing disaccharide trehalose is used as a stabilizer and humectant in various products and is a potential medicinal drug, showing curative effects on the animal models of various diseases. However, its use is limited as it is hydrolyzed by trehalase, a widely expressed enzyme in multiple organisms. Several trehalose analogs are prepared, including a microbial metabolite 4‐trehalosamine, and their high biological stability is confirmed. For further analysis, 4‐trehalosamine is selected as it shows high producibility. Compared with trehalose, 4‐trehalosamine exhibits better or comparable protective activities and a high buffer capacity around the neutral pH. Another advantage of 4‐trehalosamine is its chemical modifiability: simple reactions produce its various derivatives. Labeled probes and detergents are synthesized in one‐pot reactions to exemplify the feasibility of their production, and their utility is confirmed for their respective applications. The labeled probes are used for mycobacterial staining. Although the derivative detergents can be effectively used in membrane protein research, long‐chain detergents show 1000–3000‐fold stronger autophagy‐inducing activity in cultured cells than trehalose and are expected to become a drug lead and research reagent. These results indicate that 4‐trehalosamine is a useful trehalose substitute for various purposes and a material to produce new useful derivative substances.