脱氢氨基酸的合成及其在药物研发中的应用

Synthesis of Dehydroamino Acids and Their Applications in the Drug Research and Development

传统多肽所具有的容易被酶解、细胞膜通透性差以及构象容易发生变化等缺点,限制了它作为药物在疾病治疗领域的应用。将脱氢氨基酸引入多肽,对其进行构象限制,能够有效改善它的代谢稳定性和生物利用度。本文主要综述了α,β-脱氢-α-氨基酸、β,γ-脱氢-α-氨基酸、α-脱氢-β-氨基酸、α,β-脱氢-β-氨基酸四种脱氢氨基酸的合成方法以及近几年来在药物设计中的应用,希望为相关的研究提供参考。

Traditional polypeptides usually have the disadvantages of easy hydrolyzation,poor cell membrane permeability,and unstable conformation,which limits their application as a drug in the field of disease treatment.The conformational restriction caused by incorporation of dehydroamino acids into polypeptide can effectively improve the metabolic stability and bio availability of peptides.In this paper,the synthesis methods and the recent applications in drug design of four kinds of dehydro amino acids including α,β-dehydro-α-amino acids,β,γ-dehydro-α-amino acids,α-dehydro-β-amino acids and α,β-dehydro-β-amino acids are reviewed,which could provide reference for the related research.