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Cyclization of PLP139-151 peptide reduces its encephalitogenic potential in experimental autoimmune encephalomyelitis
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2017-12-19 , DOI: 10.1016/j.bmc.2017.12.024
Athanasios Lourbopoulos , Minos-Timotheos Matsoukas , Maria Katsara , George Deraos , Aggeliki Giannakopoulou , Roza Lagoudaki , Nikolaos Grigoriadis , John Matsoukas , Vasso Apostolopoulos

We report the novel synthesis of cyclic PLP139-151 (cPLP) and its application in SJL/J mice to study its encephalitogenic effects. Our results indicate that the cPLP analog is minimally encephalitogenic when administered to induce experimental autoimmune encephalomyelitis (low disease burden, minimal inflammatory, demyelinating and axonopathic pathology compared to its linear counterpart). Proliferation assays confirmed the low stimulatory potential of the cPLP compared to linPLP (2.5-fold lower proliferation) as well as inducing lower antibody responses. Molecular modeling showed a completely different TCR recognition profile of cPLP in regard to linPLP, where H147 replaces W144 and F151-K150 replace H147 as TCR contacts, which may explain the difference on each peptide’s response.



中文翻译:

PLP 139-151肽的环化可降低其在实验性自身免疫性脑脊髓炎中的脑潜力

我们报告了环状PLP 139-151(cPLP)的新型合成及其在SJL / J小鼠中的应用,以研究其致脑病作用。我们的结果表明,当cPLP类似物被诱导诱发实验性自身免疫性脑脊髓炎时,其致脑病作用最小(与线性对应物相比,疾病负担低,炎症,脱髓鞘和轴索病理性疾病的发生率低)。增殖测定证实与linPLP相比,cPLP的刺激潜力低(增殖低2.5倍),并诱导了较低的抗体应答。分子建模显示,与linPLP相比,cPLP的TCR识别特性完全不同,其中H 147代替W 144,F 151 -K 150代替HTCR接触为147,这可能解释了每种肽反应的差异。

更新日期:2017-12-19
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