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Cell-penetrating peptides (CPPs) are short peptides that facilitate cellular uptake of various molecular cargo (from nanosize particles to small chemical molecules and large fragments of DNA). The "cargo" is associated with the peptides either through chemical linkage via covalent bonds or through non-covalent interactions. The function of the CPPs are to deliver the cargo into cells, a process that commonly occurs through endocytosis with the cargo delivered to the endosomes of living mammalian cells. CPPs hold great potential as ''in vitro'' and ''in vivo'' delivery vectors for use in research and medicine. Current use is limited by a lack of cell specificity in CPP-mediated cargo delivery and insufficient understanding of the modes of their uptake. CPPs typically have an amino acid composition that either contains a high relative abundance of positively charged amino acids such as lysine or arginine or has sequences that contain an alternating pattern of polar/charged amino acids and non-polar, hydrophobic amino acids. These two types of structures are referred to as polycationic or amphipathic, respectively. A third class of CPPs are the hydrophobic peptides, containing only apolar residues, with low net charge or have hydrophobic amino acid groups that are crucial for cellular uptake.〔Milletti F (2012) Cell-penetrating peptides: classes, origin, and current landscape. Drug Discov Today 17: 850–860.〕〔Stalmans, Sofie; Wynendaele, Evelien; Bracke, Nathalie; Gevaert, Bert; D'Hondt, Matthias; Peremans, Kathelijne; Burvenich, Christian; De Spiegeleer, Bart. Chemical-Functional Diversity in Cell-Penetrating Peptides.PLOS ONE Volume: 8 Issue: 8 Article Number: e71752〕 The first CPP was discovered independently by two laboratories in 1988, when it was found that the trans-activating transcriptional activator (TAT) from human immunodeficiency virus 1 (HIV-1) could be efficiently taken up from the surrounding media by numerous cell types in culture.〔Protein Transduction: Cell Penetrating Peptides and Their Therapeutic Applications; Wagstaff, Kylie M.; Jans, David A; Current Medicinal Chemistry, Volume 13, Number 12, May 2006 , pp. 1371-1387(17)〕 Since then, the number of known CPPs has expanded considerably and small molecule synthetic analogues with more effective protein transduction properties have been generated.〔Okuyama, M. and Laman, H. and Kingsbury, S.R. and Visintin, C. and Leo, E. and Eward, K.L. and Stoeber, K. and Boshoff, C. and Williams, G.H. and Selwood, D.L. (2007) Small-molecule mimics of an α-helix for efficient transport of proteins into cells. Nature Methods, 4 (2). pp. 153-159〕 ==Mechanisms of membrane translocation== Cell-penetrating peptides are of different sizes, amino acid sequences, and charges but all CPPs have one distinct characteristic, which is the ability to translocate the plasma membrane and facilitate the delivery of various molecular cargoes to the cytoplasm or an organelle. There has been no real consensus as to the mechanism of CPP translocation, but the theories of CPP translocation can be classified into three main entry mechanisms: direct penetration in the membrane, endocytosis-mediated entry, and translocation through the formation of a transitory structure. CPP transduction is an area of ongoing research. 〔. Opalinska, J. B.; Gewirtz, A. M. Nucleic-acid therapeutics: basic principles and recent applications. Nat. Rev. Drug Discov. 2002, 1, 503-514〕 〔Eckstein, F. The versatility of oligonucleotides as potential therapeutics. Expert. Opin. Biol. Ther. 2007, 7, 1021-1034.〕 Cell-penetrating peptides (CPP) are able to transport different types of cargo molecules across plasma membrane; thus, they act as molecular delivery vehicles. Cell-penetrating peptides have found numerous applications in medicine as drug delivery agents in the treatment of different diseases including cancer and virus inhibitors, as well as contrast agents for cell labeling. Examples of the latter include acting as a carrier for GFP, MRI contrast agents, or quantum dots. 〔Stewart, K., M., Hortonb, K., L., O. Kelley S., O., Org. Biomol. Chem., 2008, 6, 2242–2255〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Cell-penetrating peptide」の詳細全文を読む スポンサード リンク
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