Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells.The all-hydroc...Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells.The all-hydrocarbon peptide stapling technique has already widely adopted with great success,yielding numerous potent peptide-based molecules.Based on our prior efforts,we conceived and prepared a double-stapled peptide in this study,termed FRNC-1,which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β.The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form.Additionally,FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized(OVX)mice after intravenous injection and importantly,after oral(intragastric)administration.The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis(PMOP).展开更多
基金supported by Shanghai Rising-Star Program(to Xiang Li)the National Nature Science Foundation of China No.21807112(to Xiang Li),No.91849129(to Honggang Hu),No.22077078(to Honggang Hu)and No.22207065(to Yulei Li)+1 种基金academic promotion program of Shandong First Medical University(No 2019LJ003,China,to Yulei Li)Taishan Scholars Program(to Yulei Li)。
文摘Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells.The all-hydrocarbon peptide stapling technique has already widely adopted with great success,yielding numerous potent peptide-based molecules.Based on our prior efforts,we conceived and prepared a double-stapled peptide in this study,termed FRNC-1,which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β.The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form.Additionally,FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized(OVX)mice after intravenous injection and importantly,after oral(intragastric)administration.The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis(PMOP).
