| Project/Area Number |
16310155
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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 |
Living organism molecular science
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
SUGAWARA Fumio Tokyo University of Science, Department of Applied Biological Science, Professor, 理工学部, 教授 (30192123)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥8,200,000 (Direct Cost: ¥8,200,000)
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| Keywords | anti-cancer drug / camptothecin / etoposide / phage display / binding protein / receptor / SPR / QCM / 医薬 / FKBP / 抗癌剤 / プロスタグランディン / G-タンパク質 / 表面プラズモン共鳴 / クオーツマイクロバランス振動法 / オーファン受容体 / EP1 / E2F |
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| Research Abstract |
This research subject aimed to develop new and facile methods to identify drug targeted binding proteins.
In 2004 and 2005, we studied on two anti-cancer drugs, camptothecin and etoposide as ligand to identify the binding proteins as receptors. The affinities between drug small molecules and binding proteins have been applied for our phase display screenings, which will give us high affinity phage particles displaying drug binding proteins and/or peptides. Based on the cDNA sequence data composed of the selected phages, the homology search with BLAST or FASTA program informed us that camptothecin receptor can be a prostaglandin receptor EP1 and etoposide receptor can be a transcription factor E2F. We established those bindings by SPR (surface plasmon resonance) and/or QCM (quartz crystal micro balance).
In 2006, we improved two methods. First, we employed PEG (polyethylene glycerol) beads for organic synthesis to avoid non-specific bindings between drug and proteins. Second, we immobilized ligand on a gold QCM sensor chip to afford "self-assembled membrane". In either case, we successfully identified FKBP12 as a receptor of SLF as a ligand.
Overall, we have successfully identified new target molecules of anti-cancer drugs with our improved methods. It can be expected to identify both binding proteins and receptors for drugs and other biological important small molecules.
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