領域名 生物分子化学   

教員氏名　 柳　田　　亮

研究分野 ケミカルバイオロジー

研究キーワード：天然物，発がんプロモーター，アナログ合成

最近の研究課題

1. 新規機能性を持つ発がんプロモーターアナログの開発

　発がんプロモーターとは，潜在的腫瘍細胞をクローナルに増殖させ腫瘍形成を促進する化合物の総称である．最近，天然の発がんプロモーターの構造を改変することで，望ましい機能性を持つ新規アナログの開発が行われている．我々の研究室では，抗腫瘍性化合物やがん化機構を探るツールの創製を目指して，アメフラシ由来のアプリシアトキシンやセリ科植物由来のタプシガルギンといった天然発がんプロモーターの単純化アナログの開発を行っている

2. 抗腫瘍性を示す新規プロテインキナーゼ C リガンドの探索

プロテインキナーゼC (PKC) は，がんやアルツハイマー病，HIV 治療薬の標的として注目されている．我々の研究室では，合成 PKC C1ペプチドを使って，様々な植物ソースから新規 PKC 活性化剤の探索を行っている．

3. 希少糖を基にした新規機能性分子の開発

　天然に稀にしか存在しない単糖とその誘導体の中には，がん細胞に対する増殖抑制活性など有用な生物活性を示すものがあることがこれまで報告されている．我々の研究室では，希少糖の誘導体化によるがん細胞増殖抑制活性の向上，分子プローブ化による作用機構の解明を目指して研究を進めている．

代表的な研究業績

• Ueno, S., et al. Identification and Biological Activities of Bryostatins from Japanese Bryozoan. Biosci. Biotechnol. Biochem. 2012, 76, 1041–1043.
• Yanagita, R. C., et al. Effects of the methoxy group in the side chain of debromoaplysiatoxin on its tumor-promoting and anti-proliferative activities. Bioorg. Med. Chem. Lett. 2013, 23, 4319–4323.
• Yanagita, R. C., et al. Anti-proliferative activity of 6-O-acyl-D-allose against the human leukemia MOLT-4F cell line. Biosci. Biotechnol. Biochem. 2014, 78, 190–194.
• Ashida, Y., et al. Binding mode prediction of aplysiatoxin, a potent agonist of protein kinase C, through molecular simulation and structure–activity study on simplified analogs of the receptor-recognition domain. Bioorg. Med. Chem. 2016, 24, 4218–4227.

Research Area:　Biological Molecular Chemistry
Research Specialization:　Chemical Biology　
Name:　YANAGITA, Ryo C.

Keywords：Natural product，tumor promoter，analog synthesis

Recent Research

1.Development of simplified analogs of naturally-occurring tumor promoters

　Tumor promoters are compounds which enhance tumorigenesis in cells initiated by a carcinogen.  Recently, design and synthesis of simplified analogs of naturally-occurring tumor promoters with desirable therapeutic effects including anticancer effect have been reported.

     We are currently studying on the development of simplified analogs of aplysiatoxin, a polyacetate isolated from sea hare, and thapsigargin, a sesquiterpene lactone isolated from Apiaceae plant, being synthetically accessible and having less side effect.

2.    Screening of new protein kinase C ligands with anti-proliferative activity

     Protein kinase C (PKC) is a family of serine/threonine kinase that involves in many cellular function, and are attracted as potential therapeutic target for the treatment of cancer, Alzheimer’s disease, and AIDS.

     We are searching for new PKC ligands from plant sources by an assay using synthetic PKC C1 peptides.

3.Development of biologically active derivatives of naturally-rare monosaccharide

     Several of naturally-occurring monosaccharides are found to exhibit biological activities including anti-cancer activity. We currently focus our attention on the development of rare monosaccharide derivatives with “unnatural” moiety to improve their cell permeability and biological activities.

Publications

Ueno, S., et al. Identification and Biological Activities of Bryostatins from Japanese Bryozoan. Biosci. Biotechnol. Biochem. 2012, 76, 1041–1043.

Yanagita, R. C., et al. Effects of the methoxy group in the side chain of debromoaplysiatoxin on its tumor-promoting and anti-proliferative activities. Bioorg. Med. Chem. Lett. 2013, 23, 4319–4323.
Yanagita, R. C., et al. Anti-proliferative activity of 6-O-acyl-D-allose against the human leukemia MOLT-4F cell line. Biosci. Biotechnol. Biochem. 2014, 78, 190–194.

Ashida, Y., et al. Binding mode prediction of aplysiatoxin, a potent agonist of protein kinase C, through molecular simulation and structure–activity study on simplified analogs of the receptor-recognition domain. Bioorg. Med. Chem. 2016, 24, 4218–4227.