Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,...Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,the human skeletal muscle-specific ssDNA aptamers(HSM01,etc.)were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment(SELEX).The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro.The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells.Furthermore,the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo,suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes.Therefore,this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.展开更多
Tetralin-1-carboxamides are frequently incorporated in myriad medicinally important molecules.However,their existing synthetic routes not only suffer from some drawbacks such as tedious procedures,harsh reaction condi...Tetralin-1-carboxamides are frequently incorporated in myriad medicinally important molecules.However,their existing synthetic routes not only suffer from some drawbacks such as tedious procedures,harsh reaction conditions,narrow substrate scope,low yields,and environmental problems,but are also based upon the elaboration of uneasily available non-linear tetralin derivatives.Herein,we describe a metal-and additive-free visible light-induced[4+2]annulation of two simple linear starting materials,namely acrylamides and 2-benzyl-2-bromocarbonyls,through a cascade C(sp^(3))-Br/C(sp^(2))-H bond cleavage,double C-C bond formation,and aromatization sequence.The developed protocol provides a convenient,efficient,and green approach to a variety of tetralin-1-carboxamide derivatives with good functional group compatibility.Importantly,the resulting products could also undergo the Licl-mediated mono-decarboxylative cyclization process to further furnish the architecturally novel bridged polycyclic imides with excellentcis-diastereoselectivities.展开更多
基金supported by the National Key Research and Development Plan(2018YFC2001500)National Natural Science Foundation of China(81972254,82172098).
文摘Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,the human skeletal muscle-specific ssDNA aptamers(HSM01,etc.)were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment(SELEX).The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro.The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells.Furthermore,the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo,suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes.Therefore,this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.
基金supported by the National Natural Science Foundation of China(Nos.22101237,22171233)the Science and Technology Program of Sichuan Province(Nos.2022YFS0608,2022NSFSC1219)+1 种基金the Open Project Program of Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province(Nos.HYX21003,HYX22008)the research fund of Southwest Medical University(2021ZKMS042).
文摘Tetralin-1-carboxamides are frequently incorporated in myriad medicinally important molecules.However,their existing synthetic routes not only suffer from some drawbacks such as tedious procedures,harsh reaction conditions,narrow substrate scope,low yields,and environmental problems,but are also based upon the elaboration of uneasily available non-linear tetralin derivatives.Herein,we describe a metal-and additive-free visible light-induced[4+2]annulation of two simple linear starting materials,namely acrylamides and 2-benzyl-2-bromocarbonyls,through a cascade C(sp^(3))-Br/C(sp^(2))-H bond cleavage,double C-C bond formation,and aromatization sequence.The developed protocol provides a convenient,efficient,and green approach to a variety of tetralin-1-carboxamide derivatives with good functional group compatibility.Importantly,the resulting products could also undergo the Licl-mediated mono-decarboxylative cyclization process to further furnish the architecturally novel bridged polycyclic imides with excellentcis-diastereoselectivities.
