The immunomodulatory effects of Suppressor of Cytokine Signaling (SOCS) proteins, that control the JAK/STAT pathway, indicate them as attractive candidates for immunotherapies. Recombinant SOCS3 protein suppresses the effects of inflammation, and its deletion in neurons or in immune cells increases pathological blood vessels growth. Recently, on the basis of the structure of the ternary complex among SOCS3, JAK2, and gp130, we focused on SOCS3 interfacing regions and designed several interfering peptides (IPs) that were able to mimic SOCS3 biological role in triple negative breast cancer (TNBC) models. Herein, to explore other protein regions involved in JAK2 recognition, several new chimeric peptides connecting noncontiguous SOCS3 regions and including a strongly aromatic fragment were investigated. Their ability to recognize the catalytic domain of JAK2 was evaluated through MST (microscale thermophoresis), and the most promising compound, named KIRCONG chim, exhibited a low micromolar value for dissociation constant. The conformational features of chimeric peptides were analyzed through circular dichroism and NMR spectroscopies, and their anti-inflammatory effects were assessed in cell cultures. Overall data suggest the importance of aromatic contribution in the recognition of JAK2 and that SOCS3 peptidomimetics could be endowed with a therapeutic potential in diseases with activated inflammatory cytokines.

中文翻译：

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SOCS 3的嵌合肽模拟物能够与JAK2相互作用作为抗炎化合物。

控制JAK / STAT途径的细胞因子信号转导（SOCS）蛋白抑制剂的免疫调节作用表明它们是免疫疗法的诱人候选物。重组的SOCS3蛋白可抑制炎症，其在神经元或免疫细胞中的缺失会增加病理性血管的生长。最近，基于SOCS3，JAK2和gp130之间的三元复合物的结构，我们关注SOCS3接口区域并设计了几种能够模拟SOCS3在三阴性乳腺癌（TNBC）中的生物学作用的干扰肽（IP）。楷模。在本文中，为了探索与JAK2识别有关的其他蛋白质区域，研究了几种连接非连续SOCS3区域并包括强芳香片段的新型嵌合肽。通过MST（微型热泳）评估了它们识别JAK2催化结构域的能力，最有前途的化合物KIRCONG chim表现出较低的解离常数微摩尔值。通过圆二色性和NMR光谱分析嵌合肽的构象特征，并在细胞培养物中评估其抗炎作用。总体数据表明芳烃在识别JAK2中的重要性，而SOCS3肽模拟物在具有激活的炎性细胞因子的疾病中可能具有治疗潜力。通过圆二色性和NMR光谱分析嵌合肽的构象特征，并在细胞培养物中评估其抗炎作用。总体数据表明芳烃在识别JAK2中的重要性，而SOCS3肽模拟物在具有激活的炎性细胞因子的疾病中可能具有治疗潜力。通过圆二色性和NMR光谱分析嵌合肽的构象特征，并在细胞培养物中评估其抗炎作用。总体数据表明芳烃在识别JAK2中的重要性，而SOCS3肽模拟物在具有激活的炎性细胞因子的疾病中可能具有治疗潜力。