免疫抑制剂肽Abu-TGIRIS-Abu-NH及其在多发性硬化症治疗中的应用。

Immunosuppressant Peptide Abu-TGIRIS-Abu-NH and its Application for Treatment of Multiple Sclerosis.

作者信息

Turobov Valery I, Azev Viatcheslav N, Shevelev Alexei B, Pozdniakova Natalia V, Biryukova Yulia K, Murashev Arkady N, Lipkin Valery M, Udovichenko Igor P

机构信息

1 Laboratory of Protein Chemistry, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino, 142290 Russia.

2Emanuel Institute of Biochemical Physics, Moscow, Russia.

出版信息

Bionanoscience. 2018;8(1):484-489. doi: 10.1007/s12668-018-0513-8. Epub 2018 Mar 2.

DOI:10.1007/s12668-018-0513-8

PMID:29600159

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5866264/

Abstract

Immunosuppressant peptide immunocortin for the first time was described in 1993. It corresponds to residues 11-20 of human Ig heavy chain (conserved motif of V domain). There are no data about production of immunocortin by proteolysis of Ig in vivo. Synthetic immunocortin in concentration ~ 10 M suppresses phagocytosis in peritoneal macrophages, ConA-dependent blast transformation of rat lymphocytes, exhibits ACTH-like neurotropic activity and was suggested as a potential drug for treatment of a multiple sclerosis (MS). Here, we report a sequence and method of synthesis of Abu-TGIRIS-Abu-NH (Abu, alpha-aminobutyric acid), an artificial analogue of immunocortin. Biological trials of peritoneally injected Abu-TGIRIS-Abu-NH gave an evidence of its better efficacy versus immunocortin in a test for suppression of the experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA) rats.

摘要

免疫抑制肽免疫皮质素于1993年首次被描述。它对应于人Ig重链的11 - 20位残基（V结构域的保守基序）。目前尚无关于体内Ig经蛋白水解产生免疫皮质素的数据。浓度约为10 M的合成免疫皮质素可抑制腹膜巨噬细胞的吞噬作用、大鼠淋巴细胞的ConA依赖性母细胞转化，表现出促肾上腺皮质激素样的神经otropic活性，并被认为是治疗多发性硬化症（MS）的潜在药物。在此，我们报告了免疫皮质素的人工类似物Abu - TGIRIS - Abu - NH（Abu，α - 氨基丁酸）的序列和合成方法。腹膜注射Abu - TGIRIS - Abu - NH的生物学试验证明，在抑制暗褐鼠（DA）实验性自身免疫性脑脊髓炎（EAE）的试验中，其疗效优于免疫皮质素。