Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Curr Opin Biotechnol. 2017 Dec;48:242-250. doi: 10.1016/j.copbio.2017.07.007. Epub 2017 Aug 5.
The ready availability of potent peptide binders for any desired target highlights their potential impact as therapeutic agents. Despite their versatility, however, peptides tend to display unfavourable pharmacological properties, such as low bioavailability, high renal clearance and proteolytic degradation rates, and low cell permeability. Fortunately, an increasing number of promising strategies to produce novel peptides and furnish pre-existing scaffolds with more drug-like properties are now becoming available. These strategies include incorporation of non-proteinogenic amino acids, tag appendage to existing peptides and grafting onto scaffolds already possessing desirable pharmacokinetic properties. As a consequence, a variety of promising bioactive macrocyclic peptides have recently been discovered highlighting the promise of this class of molecules as future medicines.
现成的强效肽配体可用于任何所需的靶标，这突出了它们作为治疗剂的潜力。然而，尽管肽具有多功能性，但它们往往表现出不理想的药理学特性，例如生物利用度低、肾清除率和蛋白水解降解率高以及细胞通透性低。幸运的是，现在越来越多有前途的生产新型肽的策略和为现有支架提供更具类药性的策略正在出现。这些策略包括非蛋白氨基酸的掺入、现有肽的标签附加和已经具有理想药代动力学特性的支架的嫁接。因此，最近发现了多种有前途的生物活性大环肽，这突显了此类分子作为未来药物的前景。
