Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy.
Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy.
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DOI：
10.2174/157340711796817913
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发表时间：
2011-09
影响因子：
--
通讯作者：
Kobayashi KS
中科院分区：
文献类型：
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作者：
Ogawa C;Liu YJ;Kobayashi KS
胞壁酰二肽（MDP）是由N-乙酰胞壁酸连接到L-Ala-D-isoGln的短氨基酸链组成的合成免疫反应性肽。它首先在细菌细胞壁肽聚糖中被鉴定为弗氏完全佐剂的活性成分。在细胞中，MDP由NOD 2检测，NOD 2是属于人类先天免疫系统的细胞质受体。NOD 2突变经常在克罗恩病（一种自身免疫性疾病）患者中观察到，这表明MDP-NOD 2途径在激活免疫中的重要性。出于这个原因，已经广泛研究了MDP及其衍生物的结构修饰，以试图增加佐剂活性并有效地增强免疫应答，用于治疗癌症和其他疾病的临床用途。本文综述了MDP及其衍生物的合成化学，并讨论了它们的药理作用和立体选择性合成。
Muramyl dipeptide (MDP) is a synthetic immunoreactive peptide consisting of N-acetyl muramic acid attached to a short amino acid chain of L-Ala-D-isoGln. It was first identified in bacterial cell wall peptidoglycan as an active component in Freund’s complete adjuvant. In the cell, MDP is detected by NOD2, a cytoplasmic receptor belonging to the human innate immune system. NOD2 mutations are frequently observed in patients with Crohn’s disease, an autoimmune disorder, suggesting the significance of the MDP-NOD2 pathway in activating immunity. For this reason, structural modifications of MDP and its derivatives have been extensively studied in an attempt to increase adjuvant activity and boost the immune response effectively for clinical use in the treatment of cancer and other diseases. This review summarizes the synthetic chemistry of MDP and its derivatives and discusses their pharmacological action and stereoselective synthesis.