Synthesis of OSW-1 Photoaffinity Probe and Its Biological Evaluation
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- Yamada Rika
- 東農工大院工
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- Takeshita Tomoya
- 東農工大院工
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- Hiraizumi Masato
- 東農工大院工
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- Narita Sho
- 東農工大院工
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- Sakurai Kaori
- 東農工大院工
Bibliographic Information
- Other Title
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- 抗癌活性天然物OSW-1のフォトアフィニティープローブの合成及び機能解析
Description
<p>OSW-1 (1) is a steroidal saponin, isolated from the bulbs of Ornithogalumn Saundersiae, which displays potent and selective anti-proliferative activity toward several types of cancer cell lines and its mechanism has been attracted. However, the mechanism of action at molecular level is still unclear. Identification of cellular targets of OSW-1 is important for elucidating its mechanism of action.</p><p> To identify OSW-1 binding proteins, we designed and synthesized a photoaffinity probe (2) based on OSW-1, which bears diazirine as a photoreactive group and an alkyne tag as a detection group. We previously showed by using NMR and X-ray structural analysis that the sterol side chain, the acyl groups on the sugar moiety formed a hydrophobic cluster. Based on our hypothesis that the hydrophobic cluster is a protein binding domain, we chose the C4’’-OH of 1, which is distant from the cluster moiety as the site of modification. We also developed the site-selective acylation method of 1 by using Me2SnCl2previously.</p><p> To develop the synthetic method, we first examined the Me2SnCl2-mediated acylation conditions to introduce the glutaryl linker which could be coupled to the lysine moiety bearing diazirine and alkyne (4) by using a model xylose derivative 3. Based on the optimized acylation condition, we synthesized 2 in 58% yield. The photoaffinity probe 2 showed a potent anti-proliferative activity toward HeLa cells (IC50= 2.7 nM), which is similar to that of 1. The photoaffinity labeling studies using 2were also presented.</p>
Journal
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- Symposium on the Chemistry of Natural Products, symposium papers
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Symposium on the Chemistry of Natural Products, symposium papers 57 (0), PosterP47-, 2015
Symposium on the Chemistry of Natural Products Steering Committee
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Details 詳細情報について
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- CRID
- 1390001288073793280
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- NII Article ID
- 130007493174
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- ISSN
- 24331856
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- Text Lang
- ja
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- Data Source
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- JaLC
- CiNii Articles
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- Abstract License Flag
- Disallowed