Highway to Cell: Selection of the Best Cell-Penetrating Peptide to Internalize the CFTR-Stabilizing iCAL36 Peptide.
Highway to Cell: Selection of the Best Cell-Penetrating Peptide to Internalize the CFTR-Stabilizing iCAL36 Peptide.
复制标题
通往细胞的公路：选择最佳的细胞穿透肽来内化cftr稳定iCAL36肽。
DOI：
10.3390/pharmaceutics14040808
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发表时间：
2022-04-07
期刊：
影响因子：
5.4
通讯作者：
Boisguerin, Prisca
中科院分区：
文献类型：
--
作者：
Seisel, Quentin;Lakumpa, Israpong;Josse, Emilie;Vives, Eric;Varilh, Jessica;Taulan-Cadars, Magali;Boisguerin, Prisca
关键词：
Therapeutic peptides have regained interest as they can address unmet medical needs and can be an excellent complement to pharmaceutic small molecules and other macromolecular therapeutics. Over the past decades, correctors and potentiators of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride ion channel causing cystic fibrosis (CF) when mutated, were developed to reduce the symptoms of the patients. In this context, we have previously designed a CFTR-stabilizing iCAL36 peptide able to further increase the CFTR amount in epithelial cells, thereby resulting in a higher CFTR activity. In the present study, optimization of the peptidyl inhibitor was performed by coupling five different cell-penetrating peptides (CPP), which are Tat, dTat, TatRI (retro-inverso), MPG, and Penetratin. Screening of the internalization properties of these CPP-iCAL36 peptides under different conditions (with or without serum or endocytosis inhibitors, etc.) was performed to select TatRI as the optimal CPP for iCAL36 delivery. More importantly, using this TatRI-iCAL36 peptide, we were able to reveal for the first time an additive increase in the CFTR amount in the presence of VX-445/VX-809 compared to VX-445/VX-809 treatment alone. This finding is a significant contribution to the development of CFTR-stabilizing peptides in addition to currently used treatments (small-molecule correctors or potentiators) for CF patients.
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影响因子：
7.3
作者：
Dougherty PG;Wellmerling JH;Koley A;Lukowski JK;Hummon AB;Cormet-Boyaka E;Pei D
通讯作者：
Pei D
影响因子：
7.3
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通讯作者：
Madden, Dean R.
影响因子：
4.8
作者：
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通讯作者：
Prochiantz, A