环状肽/拟肽通透性的改善：骨架-甲基化为一种有用的工具。

State Key Laboratory of Chemical Oncogenomics and Laboratory of Chemical Genomics, Engineering Laboratory for Chiral Drug Synthesis, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

Shenzhen Bay Laboratory, Shenzhen 518055, China.

Mar Drugs. 2021 May 27;19(6):311. doi: 10.3390/md19060311.

Peptides have a three-dimensional configuration that can adopt particular conformations for binding to proteins, which are well suited to interact with larger contact surface areas on target proteins. However, low cell permeability is a major challenge in the development of peptide-related drugs. In recent years, backbone -methylation has been a useful tool for manipulating the permeability of cyclic peptides/peptidomimetics. Backbone -methylation permits the adjustment of molecule's conformational space. Several pathways are involved in the drug absorption pathway; the relative importance of each -methylation to total permeation is likely to differ with intrinsic properties of cyclic peptide/peptidomimetic. Recent studies on the permeability of cyclic peptides/peptidomimetics using the backbone -methylation strategy and synthetic methodologies will be presented in this review.

肽具有三维构象，可以采用特定的构象与蛋白质结合，非常适合与靶蛋白上的更大接触面积相互作用。然而，低细胞通透性是开发肽类相关药物的主要挑战。近年来，主链甲基化已成为一种操纵环状肽/类肽通透性的有用工具。主链甲基化允许调整分子的构象空间。药物吸收途径涉及多个途径；每个 -甲基化对总通透性的相对重要性可能因环状肽/类肽的固有特性而异。本综述将介绍使用主链甲基化策略和合成方法研究环状肽/类肽通透性的最新研究。