指形龙隙蛛毒腺中抗凝活性多肽挖掘
Discovery of Anticoagulant Active Peptides from the Venom Glands of the Draconarius digitusiformis
黄彪 1温巧 1龙承波 1谷陟欣1
作者信息
- 1. 成都佩德生物医药有限公司 成都 610219
- 折叠
摘要
目的:有毒动物毒腺分泌大量结构多样和功能丰富的活性多肽,是多肽药物开发的天然宝库.目前仅有一小部分有毒动物活性多肽被研究,因此有必要建立一种更加高效的活性多肽挖掘方法.方法:以指形龙隙蛛为研究对象,通过对毒腺样本进行转录组测序、数据分析与多肽挑选,多肽重组表达制备,体外活性筛选和动物模型体内活性评价等方法,进行抗凝活性多肽的开发.结果:筛选到一种凝血因子Xa抑制剂PDBPE-001,多肽分子量为9 889.82 Da,由92个氨基酸残基组成,有4对二硫键.该多肽可通过重组表达的方式高效制备,对凝血因子Xa的抑制活性呈浓度依赖性,其半抑制浓度约为0.807 μmol/L.在体内血栓模型中,30 mg/kg PDBPE-001能起到良好的抗血栓效果.结论:首次从指形龙隙蛛中获得了一个新型Factor Xa抑制剂,为新型抗凝血药物开发提供了一个全新的先导多肽分子.
Abstract
Objective:The venom glands of toxic animals secrete a large number of structurally diverse and functionally rich active peptides,representing a natural treasure trove for peptide drug development.At present,only a small portion of the active peptides from toxic animals have been studied,so there is a need to establish a more efficient method of active peptide discovery.Methods:The anticoagulant peptides were developed by transcriptome sequencing,data analysis and polypeptide selection,peptide preparation by recombinant expression,in vitro activity screening,and in vivo activity evaluation in animal models of the Draconarius digitusiformis.Results:PDBPE-001,an inhibitor of coagulation Factor Xa,was screened.The peptide has a molecular weight of 9 889.82 Da,consisting of 92 amino acid residues and 4 pairs of disulfide bonds.This peptide can be efficiently prepared through recombinant expression,and its inhibitory activity against Factor Xa is concentration dependent,with an IC50～0.807 μmol/L.In the mouse thrombus model,30 mg/kg of PDBPE-001 has a good anti-thrombotic effect.Conclusions:A novel Factor Xa inhibitor has been obtained for the first time from the Draconarius digitusiformis,providing a new lead peptide molecule for the development of new anticoagulants.
关键词
有毒动物/活性多肽/凝血因子Xa/抗凝血药物Key words
Toxic animals/Active peptides/Factor Xa/Anticoagulants引用本文复制引用
出版年
2024
NETL
NSTL
万方数据