1998 Fiscal Year Final Research Report Summary
STUDY OF BINDING ABILITY OF PHOSPHOROTHIOATE OLIGONUCLEOTIDES WITH PROTEIN
| Project/Area Number |
08670540
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
SHOJI Yoko St.Marianna University School of Medicine Department of Microbiology, Assistant Professor, 医学部, 講師 (00235714)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUSHIMA Yutaka St.Marianna University School of Medicine Institute of Medical Science, Professo, 難病治療研究センター, 教授 (40010409)
SHIMADA Jingoro St.Marianna University School of Medicine Department of Microbiology, Professor, 医学部, 教授 (50056701)
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| Project Period (FY) |
1996 – 1998
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| Keywords | oligonucleotides / phosphorothioate / phosphodiester / anti-herpetic activities / cationic liposomes |
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| Research Abstract |
We've recognized that phosphorothioate oligonucleotides (S-ODN) showed potent anti-herpetic activities when target site was limited near the splicing site. It was implied that S-ODN interfered the conservative structure which could be essential for the splicing, thus showed potent anti-herpetic activities. This was one explanation why S-ODN targeted splicing site showed potent anti-herpetic activities. However, it has been reported that G rich sequences reveal sequence non-specific biological activities. S-ODN may reveal another mechanism which might be based on strong protein binding activities. S-ODN strongly bound to serum protein at the ratio of 86.6%, while 21.6% for phosphodiester oligonucleotides (D-ODN). Binding activities which directly bound to the virus was more than 50% for S-ODN, on the other hand it was less than 5% for D-ODN.
Thirteen mer S-ODN showed inhibitory effect on virus entry into the cell at the early stage of infection, while D-ODN did not. CD spectrum of S-ODN implied G-quartet structure, however, the relation between biological activities and higher dimension structure could not be clear.
Moreover, we tried to enhance the anti-herpetic activities of S-ODN by using cationic liposomes. Cationic liposomes is useful tool to enhance the anti-herpetic activities of D-ODN, while it was not the case for SOD.One of the reason might be strong protein binding activities of S-ODN.From this study, the caution is proposed when S-ODN containing G-rich sequences might involve another mechanism other than antisense manner. We should carefully select the drug delivery system to enhance the biological activities of S-ODN.
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