Studies on inhibitors of protein phosphatases and of protein isoprenylation, derived from Australian marine organisms
Grant-in-Aid for Overseas Scientific Survey.
|Allocation Type||Single-year Grants |
|Section||Special Cancer Research|
|Research Institution||Saitama Cancer Center |
FUJIKI Hirota Vice director, Saitama Cancer Center Research Institute, 副所長 (60124426)
MURPHY P. Chief, Australian Institute of Marine Science, 部長
QUINN R.J. Director, Queensland Pharmaceutical Research Institute School of Science, Griffi, 薬理学研究所, 所長
BAKER J. Director, Australian Institute of Marine Science, 所長
SUGANUMA Masami Researcher, Saitama Cancer Center Research Institute, 血清ウィルス部, 研究員 (20196695)
FUSETANI Nobuhiro Professor, Laboratory of Marine Biochemistry Faculty of Agriculture, The Univers, 教授 (70012010)
|Project Period (FY)
Completed (Fiscal Year 1993)
|Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1993: ¥3,200,000 (Direct Cost: ¥3,200,000)
|Keywords||Marine natural products / Protein phosphatase / protein isoprenylation / okadaic acid / anti-oxidant / Australia / anti-cancer agents / Computer graphics|
1. Research purpose
In collaboration with Dr.Joe Baker, Australian Institute of Marine Science and Dr.Ronald Quinn, Griffith University, we studied mechanisms of carcinogenesis and inhibition of carcinogenesis using Australian marine natural products for the past three years. Based on these successful collaborations, we have instigated several new projects this time, for example, screening for okadaic acid class tumor promoters, anti-okadaic acid class compound, the antioxidants and inhibitors of protein isoprenylation. In addition, we have been studying a general model of the okadaic acid class tumor promoters using a computer analysis.
Several important results are summarized.
1. We studied protein phosphatase 2A activity of 24 fractions of Australian marine organisms. One fraction isolated from marine sponge showed stimulation of protein phosphatase 2A. The extract at a concentration of 1 mg/ml enhanced the PP2A activity 4 times. The effect was contrary to that of okadaic acid, suggesting that the extract has inhibitory effect on a tumor promoter, okadaic acid. We are now isolating active principles from the extract.
2. The computer-assisted molecular modeling revealed that three okadaic acid class tumor promoters have a catalytic part and a receptor binding part in common. Based on the results, we started to synthesize chimeric compounds of calyculin A and microcystin-LR. Dr.Quinn's group synthesized a chimeric compound consisting of a receptor binding part of calyculin A and a catalytic part of microcystin-LR. We are now trying to measure its activity and compare it to those of the natural compounds, calyculin A and microcystin-LR. We expect that these results will confirm our computer generated molecular model.
Report (1 results)
Research Products (34 results)