title: LDP12, a novel cell-permeable peptide derived from L1 capsid protein of the human papillomavirus.
abstract: 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.
authors.affiliation: Department of Biomedical Science and Technology, SMART Institute of Advanced Biomedical Science, RCTC, Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Korea.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Hyunjung Jade
authors.initials: HJ
authors.lastname: Lim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D036022:Capsid Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000235:genetics* / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005455:Fluorescent Antibody Technique; D005697:Galactosides; D052140:Human papillomavirus 11 / Q000235:genetics*; D006801:Humans; D007211:Indoles; D051379:Mice; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D015202:Protein Engineering / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053586:Virus Internalization / Q000187:drug effects*; D047392:beta-Cyclodextrins / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D057846:Cell-Penetrating Peptides; D005697:Galactosides; D007211:Indoles; C094776:L1 protein, Human papillomavirus type 11; D009856:Oncogene Proteins, Viral; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D001616:beta-Galactosidase; D016650:Fluorescein-5-isothiocyanate; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside