Improving oral bioavailability of cyclic peptides by N-methylation
Improving oral bioavailability of cyclic peptides by N-methylation
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DOI：
10.1016/j.bmc.2017.08.031
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发表时间：
2018-06-01
影响因子：
3.5
通讯作者：
Kessler, Horst
中科院分区：
文献类型：
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作者：
Raeder, Andreas F. B.;Reichart, Florian;Kessler, Horst
肽在制药工业中的复兴是由于它们在许多生物功能中的重要性。然而，大多数肽的低代谢稳定性和缺乏口服利用度是一定的限制。虽然代谢不稳定性通常可以通过开发含有D-氨基酸的小环肽来克服，但大多数肽的非常低的口服利用度对于某些医学应用是严重的限制。这种情况是复杂的，因为需要双重优化-生物活性和口服有效性-来克服这个问题。此外，实现口头提供的大多数简单“规则”并不普遍，只适用于有限的情况。为了提高环肽的生物活性和代谢稳定性，人们对环肽进行了许多结构修饰，其中N-烷基化修饰可能是最常见的。这篇简短的综述主要关注环肽N-甲基化在优化生物利用度策略中的作用。(C)2017作者由爱思唯尔有限公司发布
The renaissance of peptides in pharmaceutical industry results from their importance in many biological functions. However, low metabolic stability and the lack of oral availability of most peptides is a certain limitation. Whereas metabolic instability may be often overcome by development of small cyclic peptides containing D-amino acids, the very low oral availability of most peptides is a serious limitation for some medicinal applications. The situation is complicated because a twofold optimization-biological activity and oral availability-is required to overcome this problem. Moreover, most simple "rules" for achieving oral availability are not general and are applicable only to limited cases. Many structural modifications for increasing biological activities and metabolic stabilities of cyclic peptides have been described, of which N-alkylation is probably the most common. This mini-review focuses on the effects of N-methylation of cyclic peptides in strategies to optimize bioavailabilities. (C) 2017 The Authors. Published by Elsevier Ltd.