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将体外选择指向G-四倍体形成的阿普塔默,以抑制HMGB1的病理活动
Ettore Napolitano1, Andrea Criscuolo1, Claudia Riccardi1
1Department of Chemical Sciences, University of Napoli Federico II, via Cintia 21, 80126, Napoli, Italy.
Angewandte Chemie (International ed. in English)
|February 15, 2024
概括
研究人员发现了新型的G-四重复性吸收体,可以抑制高流动性组盒1 (HMGB1),这是一种涉及炎症,自身免疫性疾病和癌症的蛋白质. 的胺体,L12,显示出强烈的活性和良好的稳定性,可用于潜在的治疗用途.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 高流动性组盒1 (HMGB1) 与炎症性和自身免疫性疾病以及癌症有关.
- 需要新的抑制剂来向HMGB1的病理活动.
研究的目的:
- 发现和表征新的抗HMGB1体.
- 评估这些体的治疗潜力.
主要方法:
- 在体外选择富含瓜的寡核酸以形成G-四重复 (G4) 结构.
- 对阿帕特默折叠和稳定性的光谱,电泳和色谱分析.
- 化学发光结合试验用于评估HMGB1的识别和选择性.
- 基于细胞的测试来评估抗HMGB1活性和毒性.
主要成果:
- 鉴定出了一组针对HMGB1的G-四重复性受体.
- 适合剂,特别是那些形成二维平行G4结构的适合剂,显示出与HMGB1.1的优先结合.
- 的阿胺体,L12,表现出强大的抗HMGB1活性 (IC50~28nM),具有良好的结合亲和力.
- L12表现出高热和酶稳定性,在健康细胞中毒性低至5μM,并抑制了HMGB1诱导的细胞迁移.
结论:
- 包括L12在内的新型G-四重复性受体,有效抑制HMGB1.1.
- 由于其稳定性,功效和安全性,L12是进一步体内研究的有希望的主要候选者.
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