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

Structure, solubility, and permeability relationships in a diverse middle molecule library.
Bioorg Med Chem Lett. 2021 Feb 08;:127847
Authors: Miyachi H, Kanamitsu K, Ishii M, Watanabe E, Katsuyama A, Otsuguro S, Yakushiji F, Watanabe M, Matsui K, Sato Y, Shuto S, Tadokoro T, Kita S, Matsumaru T, Matsuda A, Hirose T, Iwatsuki M, Shigeta Y, Nagano T, Kojima H, Ichikawa S, Sunazuka T, Maenaka K
Abstract
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 to 2,000 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.
PMID: 33571648 [PubMed - as supplied by pub...

Source: Bioorganic and Medicinal Chemistry Letters - February 8, 2021 Category: Chemistry Authors: Miyachi H, Kanamitsu K, Ishii M, Watanabe E, Katsuyama A, Otsuguro S, Yakushiji F, Watanabe M, Matsui K, Sato Y, Shuto S, Tadokoro T, Kita S, Matsumaru T, Matsuda A, Hirose T, Iwatsuki M, Shigeta Y, Nagano T, Kojima H, Ichikawa S, Sunazuka T, Maenaka K Tags: Bioorg Med Chem Lett Source Type: research