| Project/Area Number |
61870023
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
細菌学
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| Research Institution | Osaka University |
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Principal Investigator |
UCHIDA Tsuyoshi Institute for Molecular and Cellular Biology, Osaka University, 細胞工学センター, 教授 (40029781)
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| Co-Investigator(Kenkyū-buntansha) |
MIWATANI Toshio Research Institute for Microbial Diseases, Osaka University, 微生物病研究所, 教授 (60029759)
KATO Iwao Faculty of Medicin, Ciba University, 医学部, 教授 (40012702)
ARAI Tadashi Institute for Biological active substances, Ciba University, 生物活性研究所, 教授 (30009419)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 1987: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1986: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | Diphtheria toxin / Siga-like toxin / Staphylococcal leukocidin / Saframycin / Selective Killing / SSPE cells / maignant cells / 志賀様毒素の同定 / 細菌毒素 / 細胞への作用 / 活性部位 |
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| Research Abstract |
Microbial toxins and products have unique charactors which are highly specific and potent damaging and targetting for sites or molecules of cells. So, we carried out fundamental studies on application of toxins for selective killing of disease cells, such as malignant cells and virus-infected cells, and for analyzing cellular functions.
Diphtheria toxin and its targetting molecule: Naked liposomes containing fragment A of diphtheria toxin can selectively kill fusing cells by infection with enveloped virus, such as subacute sclerosing panencephalitis virus- and human immuno deficiency virus- infected cells. Seven peptides(18-27 amino acids residues) of various regions of diphtheria toxin fragment B were synthesized. Only one peptide(Pro-382-Val-401) has an activity to block entry of the toxin into cell. This peptide will be useful to immunotoxins using gragment A. cDNA of non-ADP ribosylated EF2 was cloned from toxin resistant hamster cells with co-dominant character. Transfected cells w
… More
ith the cDNA showed toxin resistant. This cDNA can be applied for positive selection.
Human enterotoxinogenics E.coli and shiga-like toxin:
Colonalization factor of E.coli is found to be hydrophilic pili, and its receptor is localized on brush border of colon. Domain peptide of the pili for binding to the receptor will be synthesized and applied to protection of the infection. It is isolated that mutant cells are highly resistant specifically to shiga-like toxin. The mutant cells are useful to identify easily shiga-like toxin.
Staphylococcal leukocidin:
Sensitivity of leukocidin to myelobastic leukemia cells is much higher than that of nirmal lymphocytes. Myeloblastic leukemia mouse can be srvived more than four months by injection of leukocidin. Thus, it will be possible to use leukocidin for transplantation of patient bone marrow cells to the patient after treatment with leukocidin.
Saframycin of Streptmyces lavendulae:
Saframycin A has cell damaging activity but stimulates immunizing activity. Now, various derivatives of saframycin could be synthesized. Among of them, saframycin Yd-1-HCl block metastase of melanoma to lung and axiral lymph nodes effectively than original saframycin A. Saframycin Y3 is effective to cure S-s180 solid tumor per os than saframycin A. This saframycin Y3 still has immuno-stimulating activity. Less
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