莫杰辛:来自Bothrops moojeni毒素的第一个分解素及其在急性髓性白血病中的抗瘤活性
Gabriela de Oliveira Almeida1, Adélia Cristina Oliveira Cintra1, Thiago Abrahão Silva1
1Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
International journal of biological macromolecules
|August 28, 2024
概括
莫杰辛是一种蛇毒分解素,在急性髓性白血病 (AML) 模型中抑制癌细胞迁移和血管生成. 这项研究描述了moojecin的特征.
科学领域:
- 生物化学和分子生物学
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
背景情况:
- 解体素是向整体素的蛇毒,这些整体素对于癌细胞粘附和转移至关重要.
- 集成蛋白信号传输在急性髓性白血病 (AML) 的进展中起着重要作用.
研究的目的:
- 为了分离和表征moojecin,一个新的RGD-disintegrin从Bothropsmoojeni毒液中.
- 评估moojecin对急性髓性白血病 (AML) 细胞系 (HL-60和THP-1) 的潜在抗瘤作用.
主要方法:
- 使用C18逆相染色学分离moojecin.
- N-终端和de novo测序用于分子识别.
- 对细胞毒性,抗增殖性,抗迁移性和抗血管性活动的评估.
- 综合素结合试验和血小板聚合试验.
- 对外围血液单核细胞 (PBMCs) 的初步毒性评估.
主要成果:
- 分离了Moojecin,其分子质量为7417.84 Da.
- 莫杰辛在AML细胞系中表现出显著的抗迁移活性和剂量依赖的血管生成抑制.
- 与α5β1.1相比,对整合素αVβ3观察到更强的结合亲和力.
- 血小板聚合IC50被确定为5.039微克/毫升.
- 在测试度下,在PBMC中没有观察到细胞毒性作用或血液溶解.
结论:
- 这项研究报告了moojecin的首次隔离和表征,这是B. moojeni毒素的分解蛋白.
- 穆杰辛具有强大的抗迁移和抗血管原性,与AML治疗有关.
- 穆杰辛为AML提供了一个有前途的治疗候选药物,具有有利的初步毒性概况.
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