Yao Jin-Feng, Yang Hong, Zhao Yan-Zhi, Xue Ming
Yanjing Medical College, Capital Medical University, Beijing 101300, China.
Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Curr Drug Metab. 2018;19(11):892-901. doi: 10.2174/1389200219666180628171531.
Despite the therapeutic use of peptides is limited because of their metabolism in vivo, there are no systematic reviews explaining degradation of peptides by peptidases. This review summarizes peptidases present in the tissues and metabolic characteristics of peptides, and provides recent strategies for improving the metabolic stability of peptides.
We reviewed a number of peptidases including their functional groups, tissue localization and cleavage specificity. Given the broad distribution of peptidases in the body, several tissues, such as the liver, kidney, lung, blood, nasal epithelial cells, placenta and skin, have the capacity to metabolize peptides. We compared the metabolic characteristics of peptides in these tissues and then summarized strategies for improving peptide stability.
In addition to the primary organs including liver, kidney, gastrointestinal tract and blood involved in peptide metabolism, other organs such as the lung, skin, placenta and nasal mucosa may also play a role in peptide degradation. At present, the main measures to improve the stability of the peptide include N- and/or C-terminal modification or substitution, D-amino acid or unnatural amino acid substitution, cyclization, backbone modification, nanoparticle formulations and increased molecular mass.
This review summarized the key in vivo peptidases and their tissue distribution characteristics, and presented strategies to improve the metabolic stability and bioavailability of peptide drugs. These viewpoints will benefit the further development and utilization of peptide drugs.
尽管由于肽在体内的代谢，其治疗用途受到限制，但尚无系统综述解释肽酶对肽的降解作用。本综述总结了组织中存在的肽酶以及肽的代谢特征，并提供了提高肽代谢稳定性的最新策略。
我们综述了多种肽酶，包括它们的官能团、组织定位和切割特异性。鉴于肽酶在体内分布广泛，肝脏、肾脏、肺、血液、鼻上皮细胞、胎盘和皮肤等多种组织都有代谢肽的能力。我们比较了这些组织中肽的代谢特征，然后总结了提高肽稳定性的策略。
除了肝脏、肾脏、胃肠道和血液等参与肽代谢的主要器官外，肺、皮肤、胎盘和鼻黏膜等其他器官也可能在肽降解中发挥作用。目前，提高肽稳定性的主要措施包括N端和/或C端修饰或替换、D-氨基酸或非天然氨基酸替换、环化、主链修饰、纳米颗粒制剂和增加分子量。
本综述总结了体内关键肽酶及其组织分布特征，并提出了提高肽类药物代谢稳定性和生物利用度的策略。这些观点将有利于肽类药物的进一步开发和利用。
