Understanding how small molecules interface with amyloid fibrils at the nanoscale is of importance for developing therapeutic treatments against amyloid-based diseases. Here, we show for the first time that human isle...Understanding how small molecules interface with amyloid fibrils at the nanoscale is of importance for developing therapeutic treatments against amyloid-based diseases. Here, we show for the first time that human islet amyloid polypeptides （LAPP） in the fibrillar form are polymorphic, ambidextrous, and possess multiple periodicities. Upon interfacing with the small molecule epigallocatechin gallate （EGCG）, IAPP aggregation was rendered off-pathway and assumed a form with soft and disordered clusters, while mature IAPP fibrils displayed kinks and branching but conserved the twisted fibril morphology. These nanoscale phenomena resulted from competitive interactions between EGCG and the IAPP amyloidogenic region, as well as end capping of the fibrils by the small molecule. This information is crucial in delineating IAPP toxicity implicated in type 2 diabetes and for developing new inhibitors against amyloidogenesis.展开更多
维生素 C 又叫做 L-抗坏血酸,它对坏血症有预防和治疗作用,人类自身不能合成,必须由外界摄取。某些动物,例如鱼虾等水产动物和人类一样,也必须由外界摄取。维生素 C(V_C)主要参与胶原的形成、氧化过程和肾上腺素的形成等,因而对动物的...维生素 C 又叫做 L-抗坏血酸,它对坏血症有预防和治疗作用,人类自身不能合成,必须由外界摄取。某些动物,例如鱼虾等水产动物和人类一样,也必须由外界摄取。维生素 C(V_C)主要参与胶原的形成、氧化过程和肾上腺素的形成等,因而对动物的生存和发育是至关重要的。胶原是构成细胞间的一种物质,它含有大量的羟脯氨酸,展开更多
文摘Understanding how small molecules interface with amyloid fibrils at the nanoscale is of importance for developing therapeutic treatments against amyloid-based diseases. Here, we show for the first time that human islet amyloid polypeptides （LAPP） in the fibrillar form are polymorphic, ambidextrous, and possess multiple periodicities. Upon interfacing with the small molecule epigallocatechin gallate （EGCG）, IAPP aggregation was rendered off-pathway and assumed a form with soft and disordered clusters, while mature IAPP fibrils displayed kinks and branching but conserved the twisted fibril morphology. These nanoscale phenomena resulted from competitive interactions between EGCG and the IAPP amyloidogenic region, as well as end capping of the fibrils by the small molecule. This information is crucial in delineating IAPP toxicity implicated in type 2 diabetes and for developing new inhibitors against amyloidogenesis.
文摘维生素 C 又叫做 L-抗坏血酸,它对坏血症有预防和治疗作用,人类自身不能合成,必须由外界摄取。某些动物,例如鱼虾等水产动物和人类一样,也必须由外界摄取。维生素 C(V_C)主要参与胶原的形成、氧化过程和肾上腺素的形成等,因而对动物的生存和发育是至关重要的。胶原是构成细胞间的一种物质,它含有大量的羟脯氨酸,
