发现一种具有改进的内体逃逸和细胞质递送效率的环状细胞穿透肽。
Discovery of a Cyclic Cell-Penetrating Peptide with Improved Endosomal Escape and Cytosolic Delivery Efficiency.
机构信息
Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, United States.
出版信息
Mol Pharm. 2022 May 2;19(5):1378-1388. doi: 10.1021/acs.molpharmaceut.1c00924. Epub 2022 Apr 11.
Abstract
Cyclic cell-penetrating peptide 12 (CPP12) is highly efficient for the cytosolic delivery of a variety of cargo molecules into mammalian cells in vitro and in vivo. However, its cytosolic entry efficiency is substantially reduced at lower concentrations or in the presence of serum proteins. In this study, CPP12 analogs were prepared by replacing its hydrophobic residues with amino acids of varying hydrophobicity and evaluated for cellular entry. Substitution of l-3-benzothienylalanine (Bta) for l-2-naphthylalanine (Nal) resulted in CPP12-2, which exhibits up to 3.8-fold higher cytosolic entry efficiency than CPP12, especially at low CPP concentrations; thanks to improved endosomal escape efficiency. CPP12-2 is well suited for the cytosolic delivery of highly potent cargos to achieve biological activity at low concentrations.
摘要
环肽 12（CPP12）对于将各种货物分子高效地递送至体外和体内的哺乳动物细胞的细胞质中是非常有效的。然而，在较低浓度或存在血清蛋白的情况下，其细胞质进入效率会大大降低。在这项研究中，通过用不同疏水性的氨基酸替换 CPP12 的疏水性残基来制备 CPP12 类似物，并对其细胞进入进行了评估。用 l-3-苯并噻吩基丙氨酸（Bta）替代 l-2-萘丙氨酸（Nal）得到 CPP12-2，其细胞质进入效率比 CPP12 高 3.8 倍，尤其是在 CPP 浓度较低时；这要归功于提高了内体逃逸效率。CPP12-2 非常适合将高活性货物递送至细胞质中，以在低浓度下实现生物活性。
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1
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2
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Angew Chem Int Ed Engl. 2021 Jun 25;60(27):14824-14830. doi: 10.1002/anie.202102332. Epub 2021 May 28.
3
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Proc Natl Acad Sci U S A. 2021 May 4;118(18). doi: 10.1073/pnas.2024102118.
4
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J Med Chem. 2020 Nov 12;63(21):12853-12872. doi: 10.1021/acs.jmedchem.0c01236. Epub 2020 Oct 19.
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6
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