Che Ye
Discovery Sciences, Pfizer Inc., Groton, CT, USA.
Methods Mol Biol. 2019;2001:97-106. doi: 10.1007/978-1-4939-9504-2_6.
Protein-protein interactions are ubiquitous, essential to almost all known biological processes, and offer attractive opportunities for therapeutic intervention. Linear peptide drugs, however, can be applied therapeutically as protein recognition motifs only to a limited extent because of their poor permeability, decreased receptor selectivity, and proteolytic stability. A major strategy in peptide chemistry is directed toward chemical modification and macrocyclization in order to limit a peptide's conformational possibilities, to increase its chemical and enzymatic stability, to prolong the time of action, and to increase activity and selectivity toward the receptor.
蛋白质-蛋白质相互作用普遍存在，对几乎所有已知的生物过程都至关重要，并为治疗干预提供了诱人的机会。然而，线性肽药物作为蛋白质识别基序在治疗上的应用范围有限，因为它们的渗透性差、受体选择性降低以及蛋白水解稳定性低。肽化学中的一个主要策略是进行化学修饰和大环化，以限制肽的构象可能性，提高其化学和酶稳定性，延长作用时间，并提高对受体的活性和选择性。
