新型 2-叠氮基胞壁酰二肽的合成及作为 NOD2 激动剂佐剂的生物学评价。
Synthesis and biological evaluation of novel 2-azido muramyl dipeptide as NOD2 agonistic adjuvants.
机构信息
Vaccine Immunology Laboratory, OSPC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201 002, India.
Vaccine Immunology Laboratory, OSPC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
出版信息
Bioorg Med Chem. 2022 Jul 15;66:116781. doi: 10.1016/j.bmc.2022.116781. Epub 2022 May 2.
Novel 2-Azido muramyl dipeptide was synthesized by the bio-isosteric replacement of the N-acetyl group of the muramic acid fragment with the azide functionality at the C2 position. In order to examine the effect of hydrophilic-lipophilic balance on the adjuvant activity, derivatives were synthesized by removing protecting groups sequentially to tune the polarity. Amongst five novel azido derivatives of MDP studied here, di- and mono-benzylated azido derivatives 10 and 11 exhibited good DENV specific antibody(IgG) response with Th1 polarization compared to parent compound Muramyl dipeptide (MDP) whereas all five new derivatives responded positively to NOD2 agonistic assays with compound 10 showing highest stimulation.
新型 2-叠氮基 muramyl 二肽通过将 muramic 酸片段的 N-乙酰基用叠氮基功能团在 C2 位进行生物等排取代来合成。为了研究亲水-亲脂平衡对佐剂活性的影响，通过依次去除保护基来合成衍生物以调整极性。在研究的五种新型 MDP 叠氮衍生物中，二苄基和单苄基叠氮衍生物 10 和 11 与母体化合物 muramyl 二肽（MDP）相比，表现出良好的 DENV 特异性抗体（IgG）反应和 Th1 极化，而所有五种新型衍生物对 NOD2 激动剂检测呈阳性反应，其中化合物 10 表现出最高的刺激作用。
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