Modulating the Fibrillization of Parathyroid-Hormone (PTH) Peptides: Azo-Switches as Reversible and Catalytic Entities
BIOMEDICINES(2022)
摘要
We here report a novel strategy to control the bioavailability of the fibrillizing parathyroid hormone (PTH)-derived peptides, where the concentration of the bioactive form is controlled by an reversible, photoswitchable peptide. PTH1-84, a human hormone secreted by the parathyroid glands, is important for the maintenance of extracellular fluid calcium and phosphorus homeostasis. Controlling fibrillization of PTH1-84 represents an important approach for in vivo applications, in view of the pharmaceutical applications for this protein. We embed the azobenzene derivate 3-{[(4-aminomethyl)phenyl]diazenyl}benzoic acid (3,4 '-AMPB) into the PTH-derived peptide PTH25-37 to generate the artificial peptide AzoPTH(25-37) via solid-phase synthesis. AzoPTH(25-37) shows excellent photostability (more than 20 h in the dark) and can be reversibly photoswitched between its cis/trans forms. As investigated by ThT-monitored fibrillization assays, the trans-form of AzoPTH(25-37) fibrillizes similar to PTH25-37, while the cis-form of AzoPTH(25-37) generates only amorphous aggregates. Additionally, cis-AzoPTH(25-37) catalytically inhibits the fibrillization of PTH25-37 in ratios of up to one-fifth. The approach reported here is designed to control the concentration of PTH-peptides, where the bioactive form can be catalytically controlled by an added photoswitchable peptide.
更多查看译文
关键词
azobenzene, photoswitchable peptides, fibrillization, parathyroid hormone, aggregation
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要