Bioorganic & medicinal chemistry letters · 2021
Structure, solubility, and permeability relationships in a diverse middle molecule library.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Miyachi Hiroyuki, Kanamitsu Kayoko, Ishii Mayumi, Watanabe Eri, Katsuyama Akira, Otsuguro Satoko, Yakushiji Fumika, Watanabe Mizuki, Matsui Kouhei, Sato Yukina, Shuto Satoshi, Tadokoro Takashi, Kita Shunsuke, Matsumaru Takanori, Matsuda Akira, Hirose Tomoyasu, Iwatsuki Masato, Shigeta Yasuteru, Nagano Tetsuo, Kojima Hirotatsu, Ichikawa Satoshi, Sunazuka Toshiaki, Maenaka Katsumi
Аннотация
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.