胞壁酰二肽及其衍生物：免疫紊乱和癌症治疗中的肽佐剂
Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy.
作者信息
Ogawa Chikako, Liu Yuen-Joyce, Kobayashi Koichi S
机构信息
Eisai Research Institute, 4 Corporate drive, Andover, MA 01810.
出版信息
Curr Bioact Compd. 2011 Sep;7(3):180-197. doi: 10.2174/157340711796817913.
Abstract
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.
摘要
胞壁酰二肽（MDP）是一种合成免疫反应性肽，由连接在L-丙氨酸-D-异谷氨酰胺短氨基酸链上的N-乙酰胞壁酸组成。它最初在细菌细胞壁肽聚糖中被鉴定为弗氏完全佐剂中的活性成分。在细胞中，MDP由NOD2检测，NOD2是一种属于人类先天免疫系统的细胞质受体。在患有自身免疫性疾病克罗恩病的患者中经常观察到NOD2突变，这表明MDP-NOD2途径在激活免疫方面的重要性。因此，人们对MDP及其衍生物的结构修饰进行了广泛研究，试图提高佐剂活性并有效增强免疫反应，以便在癌症和其他疾病的治疗中临床应用。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。
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