Translocation of branched-chain arginine peptides through cell membranes: flexibility in the spatial disposition of positive charges in membrane-permeable peptides.
A basic peptide derived from HIV-1 Tat has been reported to have the ability to translocate through cell membranes and to bring exogenous proteins into cells. We have demonstrated that these features could be observed among many arginine-rich peptides, and the presence of a ubiquitous internalization mechanism for arginine-rich oligopeptides has been suggested. In this report, we report that these features are also applicable to the peptides having branched-chain structures. Peptides that have arginine residues on four branched chains (R(n))(4) [n (number of arginine residues)= 0-6] were prepared. Fluorescence microscopic observation revealed that the (R(2))(4) peptide exhibited the most efficient translocation. The dependence on the number of arginine residues of the translocation efficiency and cellular localization was also observed for the branched-chain peptides as was seen in the linear peptides. Quite interestingly, efficient translocation was also recognized in the (RG(3)R)(4) peptide, where three glycine residues intervened between two arginine residues on each chain of (R(2))(4). The results strongly suggested that a linear structure was not indispensable for the translocation of arginine-rich peptides and that there could be considerable flexibility in the location of the arginine residue in the molecules.
Futaki
Shiroh
S
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. futaki@scl.kyoto-u.ac.jp
Nakase
Ikuhiko
I
Suzuki
Tomoki
T
Youjun
Zhang
Z
Sugiura
Yukio
Y
D000595:Amino Acid Sequence; D000597:Amino Acids, Branched-Chain / Q000737:chemistry* / Q000378:metabolism*; D001120:Arginine / Q000737:chemistry* / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002463:Cell Membrane Permeability; D015696:Gene Products, tat / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D021381:Protein Transport; D013329:Structure-Activity Relationship; D054322:tat Gene Products, Human Immunodeficiency Virus
D000597:Amino Acids, Branched-Chain; D002352:Carrier Proteins; D015696:Gene Products, tat; D010446:Peptide Fragments; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus; D001120:Arginine