Structure, solubility, and permeability relationships in a diverse middle molecule library

Hiroyuki Miyachi, Kayoko Kanamitsu, Mayumi Ishii, Eri Watanabe, Akira Katsuyama, Satoko Otsuguro, Fumika Yakushiji, Mizuki Watanabe, Kouhei Matsui, Yukina Sato, Satoshi Shuto, Takashi Tadokoro, Shunsuke Kita, Takanori Matsumaru, Akira Matsuda, Tomoyasu Hirose, Masato Iwatsuki, Yasuteru Shigeta, Tetsuo Nagano, Hirotatsu KojimaSatoshi Ichikawa, Toshiaki Sunazuka, Katsumi Maenaka

研究成果: Article査読

抄録

To develop methodology to predict the potential druggability of middle molecules, we examined the structure, solubility, and permeability relationships of a diverse library (HKDL ver.1) consisting of 510 molecules (359 natural product derivatives, 76 non-natural products, 46 natural products, and 29 non-natural product derivatives). The library included peptides, depsipeptides, macrolides, and lignans, and 476 of the 510 compounds had a molecular weight in the range of 500–2000 Da. The solubility and passive diffusion velocity of the middle molecules were assessed using the parallel artificial membrane permeability assay (PAMPA). Quantitative values of solubility of 471 molecules and passive diffusion velocity of 287 molecules were obtained, and their correlations with the structural features of the molecules were examined. Based on the results, we propose a method to predict the passive diffusion characteristics of middle molecules from their three-dimensional structural features.

本文言語English
論文番号127847
ジャーナルBioorganic and Medicinal Chemistry Letters
37
DOI
出版ステータスPublished - 2021 4 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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