In silico identification and experimental validation of cellular uptake and intracellular labeling by a new cell penetrating peptide derived from CDN1

Drug Delivery

Jixiong Hu¹  Jason Li²  Xiangli Guo³  Jingping Geng³  Lidan Wang³  Hu Wang⁴  Changbai Liu⁵  Linlin Chen⁶  Tao Wang⁷ 

[1] College of Life Science, Yangtze University, Jingzhou, Chin;Department of Biology, Johns Hopkins University, Baltimore, MD, US;Department of Pathology and Immunology, Medical School, China Three Gorges University, Yichang, Chin;Hubei Key Lab of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Chin;Department of Pathology and Immunology, Medical School, China Three Gorges University, Yichang, Chin;Lead Contac;Hubei Key Lab of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Chin;Hubei Key Lab of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Chin;Affiliated Ren He Hospital of China Three Gorges University, Yichang, Chin;The First Clinical Medical College of China Three Gorges University, Yichang, Chin;

关键词: Cell-permeable peptides (CPPs);    bioinformatics;    protein delivery;    HaloTag;   

DOI  :  10.1080/10717544.2021.1963352

来源: Taylor & Francis

【 摘 要 】

Bioactive therapeutic molecules are generally impermeable to the cell membrane, hindering their utility and efficacy. A group of peptides called cell-penetrating peptides (CPPs) were found to have the capability of transporting different types of cargo molecules across the cell membrane. Here, we identified a short peptide named P2, which has a higher proportion of basic residues than the CDN1 (cyclin-dependent kinase inhibitor 1) protein it is derived from, and we used bioinformatic analysis and experimental validation to confirm the penetration property of peptide P2. We found that peptide P2 can efficiently enter different cell lines in a concentration-dependent manner. The endocytosis pathway, especially receptor-related endocytosis, may be involved in the process of P2 penetration. Our data also showed that peptide P2 is safe in cultured cell lines and red blood cells. Lastly, peptide P2 can efficiently deliver self-labeling protein HaloTag into cells for imaging. Our study illustrates that peptide P2 is a promising imaging agent delivery vehicle for future applications.

【 授权许可】

CC BY