Innovative technological development for the production of the complex crystal with high-strength hydrogel

2015 Fiscal Year Final Research Report

• Project/Area Number: 25286051
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Crystal engineering
• Research Institution: Osaka University
• Principal Investigator: SUGIYAMA SHIGERU 大阪大学, 理学(系)研究科(研究院), 准教授 (90615428)
• Co-Investigator(Renkei-kenkyūsha): MATSUMORI NOBUAKI 九州大学, 理学(系)研究科(研究院), 教授 (50314357) ; TERAI TAKUYA 東京大学, 薬学研究科(研究院), 助教 (00508145)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 結晶工学 / 結晶成長 / 脂質結合タンパク質 / 凝固ゲル / 創薬スクリーニング / Ｘ線構造解析 / 脂質 / 難水溶性化合物

Outline of Final Research Achievements

X-ray crystallography offers an unprecedented opportunity to facilitate drug discovery. The structural information of the protein-ligand complex has the potential to find ways to improve the lead compounds. The best way is to determine the three dimensional structure of the complex by soaking the ligand in crystals. However, the soaking step has a problem because many lead compounds are low water-soluble. Such lead compounds must be dissolved in concentrated organic solvents, such as dimethyl sulfoxide (DMSO). We recently developed a new method for growing crystals in a high-strength hydrogel. This method enabled us to increase the mechanical stability of the crystals. In this study, we transferred the hydrogel-grown avidin/streptavidin or FABP crystals into a 50% DMSO solution containing the inhibitors. We observed the clear electron density maps of the compounds that are bound to the active sites.

Free Research Field

生物学