2002 Fiscal Year Final Research Report Summary
Analysis of Intermedilysin in Human Specific Cytolytic Mechanism : Design and Application for Cell Targeting Module.
| Project/Area Number |
12672151
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
医薬分子機能学
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
OHKURA Kazuto Graduate School of Bioagricultural Sciences, Nagoya University Assistant Professor, 大学院・生命農学研究科, 助手 (00242850)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAGAMUNE Hideaki Faculty of Engineering, University of Tokushima Associate Professor, 工学部, 助教授 (40189163)
HORI Hitoshi Faculty of Engineering, University of Tokushima Professor, 工学部, 教授 (90119008)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Keywords | cytolysin / targeting / infection |
|---|
| Research Abstract |
Intermedilysin (ILY), a human specific cytolysin secreted by Streptococcus intermedius, is a member of the gene of SLO-family cytolysin (SFC), but differs by exhibiting a low affinity to cholesterol (CHL) in addition to human specificity. We modeled ILY molecule using perfringolysin O (PFO) X-ray data, and observed four domain (domain 1 〜 domain 4) in the molecule. From the analysis of ILY model, the domain 4 seems to be the human cell membrane associated region. Especially, extended-NTD sequence at ILY C-terminal appeared an important factor for human specific cytolysis. Indeed, the NTD-deleted ILY mutant (ΔNTD-ILY) decreased the hemolytic activity for human erythrocytes. Then we considered that the C-terminal NTD should be concerning with the cluster formation on the human cell membrane.
Moreover we constructed the antiCEA-antibody conjugated ILY domain4 (antiCEA-ILY4D), and examined the cell delivery system. AntiCEA-ILY4D bind to human erythrocyte (ET) membrane easily, and this ET-AntiCEA-ILY4D module recognized CEA-positive TT cell. Now we are improving these targeting modules.
|
-
-
-
-
-
[Publications] Goto,T., Nagamune,N., Kawamura,Y., Ohnishi,O., Hattori,K., Ohkura,K., Miyamoto.K., Akimoto,S., Ezaki,T., Hirota,K., Miyake,Y., Maeda,T.and Kourai,H.: "Rapid Identification of Streptococcus intermedius by PCR using the ily gene as aspecies marker gene"J.Med.Microbiol. 51. 178-186 (2002)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Hori,H., Nagasawa,H., Ishibashi,M., Uto,Y., Hirata,A., Saijo,K., Ohkura,K., Kirk,K.L.and Uehara,Y.: "TX-1123 : An Antitumor 2-Hydroxyarylidene-4-cyclopentene-1, 3-Dione as a Protein Tyrosine Kinase Inhibitor Having Low Mitochondrial Toxicity"Bioorg.Med.Chem.. 10. 3257-3265 (2002)
Description
「研究成果報告書概要(欧文)」より
-
-
