2003 Fiscal Year Final Research Report Summary
Design and intracellular delivery of peptides for transcription regulation
| Project/Area Number |
14370720
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
FUTAKI Shiroh Kyoto Univ., Inst. Chem. Res., Associate Prof., 化学研究所, 助教授 (50199402)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIURA Yukio Kyoto Univ., Inst. Chem. Res., Prof., 化学研究所, 教授 (40025698)
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| Project Period (FY) |
2002 – 2003
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| Keywords | signal transduction / synthetic peptide / HIV / translocation / peptide engineering / intracellular protein labeling / transcription factor / arginine |
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| Research Abstract |
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. 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. The site of action for these complexes resides in the stages between the viral entry into the cells and reverse transcription, suggesting the possibility of the recognition of viral RNA by these basic peptides in the cells. 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. As for cross-linking formation between delivered molecules and cellular proteins, the feasibility of employment of light-induced cross-linker and aldehyde moieties was assessed. However, since the efficiency of cross-linking formation was not satisfactory, we are now seeking alternative systems to resolve this problem.
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