LDP12, a novel cell-permeable peptide derived from L1 capsid protein of the human papillomavirus
We designed a novel cell-permeable peptide, LDP12, from the human papillomavirus L1 capsid protein. In this work, we examined the mechanism of cellular entry by LDP12 and its efficacy as a potential carrier of protein cargoes. The 12-mer peptide linked to FITC freely enters various types of mammalian cells within a few minutes via an endocytic pathway, as its entry is blocked at a low temperature. Several inhibitors which block certain pathway of endocytosis were used to determine which pathway is utilized by LDP12. We found that methyl-β-cyclodextrin specifically blocks LDP12 entry, suggesting that lipid raft-mediated pathway is involved. Intraluminal injection of LDP12-FITC into the mouse uterus shows that this peptide could penetrate the uterine tissue and stay as long as 24 h. Furthermore, LDP12 with a cysteamide group at the C-terminus successfully carries purified protein cargoes into mammalian cells including rat cortical neurons. Collectively, LDP12 could be utilized as a method of protein therapeutics targeting various mammalian cell types.
KeywordsCell-permeable peptide LDP12 Endocytosis Uterus Protein cargo
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No.2009-0080617). Authors thank Ms. E. B. Park for providing rat neuronal cells. We also thank members of Lim laboratory for various supports.
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