Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, PR China.
Peptides. 2011 May;32(5):1047-54. doi: 10.1016/j.peptides.2011.03.005. Epub 2011 Mar 22.
The monocyte locomotion inhibitory factor (MLIF) is an anti-inflammatory oligopeptide produced by Entamoeba histolytica. Among its different effects, it inhibits locomotion of human monocytes, hence its original name. The carboxyl-terminal end group Cys-Asn-Ser is the pharmacophore of anti-inflammatory peptide Met-Gln-Cys-Asn-Ser. In this study, the N-terminal of Cys-Asn-Ser was modified. With the aim to enhance the antioxidant ability and penetrability of Cys-Asn-Ser, we designed and synthesized two tetrapeptides Tyr-Cys-Asn-Ser and His-Cys-Asn-Ser. The neuroprotective effects of Tyr-Cys-Asn-Ser and His-Cys-Asn-Ser on focal ischemia reperfusion were investigated, and their pharmacological activities compared with Cys-Asn-Ser were studied. In order to study the mechanism of neuroprotective effect of these peptides, the level of oxidative stress markers malondialdehyde (MDA) and superoxide dismutase (SOD) and pro-inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and myeloperoxidase (MPO) were detected in brain tissue homogenate.
单核细胞迁移抑制因子（MLIF）是一种由溶组织内阿米巴产生的抗炎寡肽。在其众多作用中，MLIF 可以抑制人单核细胞的迁移，这也是其最初被命名的原因。该抗炎肽 Met-Gln-Cys-Asn-Ser 的药效基团是其羧基末端的 Cys-Asn-Ser。在本研究中，对 Cys-Asn-Ser 的 N 端进行了修饰。为了增强 Cys-Asn-Ser 的抗氧化能力和穿透性，我们设计并合成了两种四肽 Tyr-Cys-Asn-Ser 和 His-Cys-Asn-Ser。研究了 Tyr-Cys-Asn-Ser 和 His-Cys-Asn-Ser 对局灶性缺血再灌注的神经保护作用，并与 Cys-Asn-Ser 的药理活性进行了比较。为了研究这些肽的神经保护作用机制，检测了脑组织匀浆中氧化应激标志物丙二醛（MDA）和超氧化物歧化酶（SOD）以及促炎因子白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和髓过氧化物酶（MPO）的水平。
