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Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics.
Amino Acids ( IF 3.0 ) Pub Date : 2020-09-18 , DOI: 10.1007/s00726-020-02890-9
Yun Ding 1 , Joey Paolo Ting 1 , Jinsha Liu 1 , Shams Al-Azzam 2 , Priyanka Pandya 1 , Sepideh Afshar 1
Affiliation  

With the development of modern chemistry and biology, non-proteinogenic amino acids (NPAAs) have become a powerful tool for developing peptide-based drug candidates. Drug-like properties of peptidic medicines, due to the smaller size and simpler structure compared to large proteins, can be changed fundamentally by introducing NPAAs in its sequence. While peptides composed of natural amino acids can be used as drug candidates, the majority have shown to be less stable in biological conditions. The impact of NPAA incorporation can be extremely beneficial in improving the stability, potency, permeability, and bioavailability of peptide-based therapies. Conversely, undesired effects such as toxicity or immunogenicity should also be considered. The impact of NPAAs in the development of peptide-based therapeutics is reviewed in this article. Further, numerous examples of peptides containing NPAAs are presented to highlight the ongoing development in peptide-based therapeutics.



中文翻译:


非蛋白氨基酸对肽疗法发现和开发的影响。



随着现代化学和生物学的发展,非蛋白氨基酸(NPAA)已成为开发基于肽的候选药物的有力工具。与大蛋白质相比,肽类药物的尺寸更小、结构更简单,因此其类药特性可以通过在其序列中引入 NPAA 来从根本上改变。虽然由天然氨基酸组成的肽可用作候选药物,但大多数肽在生物条件下稳定性较差。 NPAA 的掺入对于提高基于肽的疗法的稳定性、效力、渗透性和生物利用度非常有益。相反,还应考虑毒性或免疫原性等不良影响。本文综述了 NPAA 在肽类疗法开发中的影响。此外,还提出了许多含有 NPAA 的肽的例子,以强调基于肽的疗法的持续发展。

更新日期:2020-09-20
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