Mizuno-Kaneko Mai, Hashimoto Ichihiko, Miyahara Kenta, Kochi Masahiro, Ohashi Noriyuki, Tsumura Kyosuke, Suzuki Koo, Tamura Takashi
Synthetic Organic Chemistry Laboratories, FUJIFILM Corporation, 577, Ushijima, Kaisei-machi, Ashigarakami-gun, Kanagawa 258-8577, Japan.
Analysis Technology Center, FUJIFILM Corporation, 210, Nakanuma, Minamiashigara-shi, Kanagawa 250-0193, Japan.
ACS Med Chem Lett. 2023 Aug 10;14(9):1174-1178. doi: 10.1021/acsmedchemlett.3c00102. eCollection 2023 Sep 14.
Cyclic peptides have been expected to be one of the modalities of intracellular protein-protein interaction (PPI) inhibitors, but they are generally known to have low cell membrane permeability. In this study, we focused on the conformation of cyclic peptides in the cell membrane to determine the requirement for their cell membrane permeability through passive diffusion. Utilizing the requirement, we searched for structures with high affinity for MDMX via computational chemistry and acquired cyclic peptide ( = 0.80 × 10 cm s, IC = 0.07 μM).
环肽有望成为细胞内蛋白质-蛋白质相互作用（PPI）抑制剂的一种形式，但众所周知，它们的细胞膜通透性通常较低。在本研究中，我们关注环肽在细胞膜中的构象，以确定其通过被动扩散实现细胞膜通透性的条件。利用这一条件，我们通过计算化学寻找与MDMX具有高亲和力的结构，并获得了环肽（= 0.80 × 10 cm s，IC = 0.07 μM）。
