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从非血液吸血的吸血虫中探索一种希鲁丁变体:解开全长序列,替代拼接,功能和作为新型抗凝聚物聚的潜力

Xiaozhe Yi¹, Jiali Liu¹, Erhuan Zang¹

¹State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China; Key Lab of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Engineering Research Center of Chinese Medicine Resource, Ministry of Education, Beijing 100193, China.

Journal of ethnopharmacology

|April 27, 2024

概括

研究人员在非血吸血的水Whitmania pigra.中发现了一种新的hirudin变体 (WP_HV1). 这种变体表现出显著的抗凝活性,为开发抗血栓治疗提供了新的途径.

科学领域:

生物化学生化学
分子生物学分子生物学
药理学药理学是指药理学的学科.

背景情况:

吸血虫以其抗凝固特性而闻名,在传统中医中用于治疗心血管疾病.
怀特马尼亚猪,中国的一个关键的水物种,拥有强大的抗凝活性,虽然它是非血的.
希鲁丁是一种强大的血栓抑制剂,通常在血液消耗的吸血虫中发现,这引发了关于其在W. pigra.中的存在的问题.

研究的目的:

在W. pigra基因组中识别编码hirudin的基因.
评估已识别的希鲁丁变体的抗凝活性.
阐明其抗凝性质背后的机制.

主要方法:

鉴定和克隆来自W. pigra.的编码希鲁丁基因 (WP_HV1).
序列和结构分析以预测血栓结合和抗凝活性.
重组WP_HV1和大肠杆菌中的突变体的表达,其次是血时间 (TT) 试验.

主要成果:

确定了WP_HV1基因,发现了三个替代拼接.
重组WP_HV1显示出显著的抗凝剂活性,延长了血时间的1.74倍.
抗凝剂活性与C终端氨酸和特定的酸性氨基酸有关;突变降低了活性,而 Lysine-67 到 Tryptophan 突变增强了活性.

结论:

在Whitmania pigra.中发现了一个编码hirudin的单个变异,WP_HV1.
该研究解决并验证了负责WP_HV1抗凝的活性氨基酸.
WP_HV1代表了开发新型抗凝血药物的新来源.

关键词:

抗凝固活性是一种抗凝固活性.希鲁丁的变体希鲁丁的变体药用吸血虫是一种药用吸血虫.血抑制剂药物血抑制剂药物怀特曼尼亚猪 (Whitmania pigra) 是一种猪类动物.

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