Montrose Kristopher, Yang Yi, Krissansen Geoffrey W
Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Biochem Biophys Res Commun. 2014 Oct 10;453(1):64-8. doi: 10.1016/j.bbrc.2014.09.057. Epub 2014 Sep 22.
Cell-penetrating peptides (CPPs) are able to penetrate the plasma membrane and gain access to the interior of any replicating or non-replicating cell, and are being considered as drug delivery agents. Here we describe the serendipitous discovery of a novel CPP motif (MAARLCCQ), designated X-pep, located at the extreme N-terminus of the X-protein of the hepatitis B virus. X-pep, and a C-terminally truncated form of the peptide (MAARL), readily penetrated HepG2 cells. Further truncation by removal of the terminal leucine residue impaired the cell-penetrating activity of peptide, indicating that MAARL is the active core of the peptide. X-pep is located adjacent to another CPP, namely Xentry, and like Xentry is unable to penetrate unactivated resting lymphocytes suggesting selective cell uptake. A D-isomeric form of the MAARL peptide was not cell-permeable, indicating that the cell-penetrating function of the peptide involves stereoselective interaction with a chiral receptor. The discovery of X-pep, which bears no resemblance to known CPPs, allows studies to be undertaken to determine additional characteristics of this novel CPP.
细胞穿透肽（CPPs）能够穿透质膜并进入任何正在复制或非复制细胞的内部，正被视为药物递送剂。在此，我们描述了一个位于乙型肝炎病毒X蛋白极端N端的新型CPP基序（MAARLCCQ）的意外发现，该基序被命名为X-肽。X-肽以及该肽的C端截短形式（MAARL）能够轻易穿透HepG2细胞。通过去除末端亮氨酸残基进一步截短会损害该肽的细胞穿透活性，这表明MAARL是该肽的活性核心。X-肽与另一种CPP即Xentry相邻，并且与Xentry一样无法穿透未活化的静止淋巴细胞，提示存在选择性细胞摄取。MAARL肽的D-异构体形式不具有细胞渗透性，这表明该肽的细胞穿透功能涉及与手性受体的立体选择性相互作用。X-肽的发现与已知的CPPs没有相似之处，这使得我们能够开展研究以确定这种新型CPP的其他特性。
