Design and intracellular delivery of peptides for transcription regulation

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A basic peptide derived from the human immunodeficiency virus (HIV)-1 Tat has been reported to have the ability to translocate through the cell membranes and to bring exogenous proteins into the cells. We have demonstrated that these features were observable among many arginine-rich peptides including those having a branched chain structure. Based on these findings, the presence of a ubiquitous internalization mechanism for the arginine-rich peptides has been suggested. We have also demonstrated 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 showed the most efficient translocation. Dependence on the number of arginine residues for the translocation efficiency and cellular localization was also observed for the branched-chain peptides as was seen in the linear peptides. We have shown that a non-covalent protein assembly of Rnase S bearing arginine-rich segment was successfully introduced into cells to exhibit an anti-HIV activity. Peptides corresponding to the phosphorylation and ubiquitilation sites of IκB, which is involved in the activation of transcription factor NF-κB, were prepared. Introduction of these peptides into cells by conjugation with the membrane-permeable arginine peptide resulted in the inhibition of NF-κB activation. However, significance of the difference in the extent of inhibition was observed. We have also shown that the transcription by transcription factor Sp1 was inhibited by the peptide derived from DNA recognition segment of Sp1.