Targeting the contact-kinin system: A cyclopeptide with anti-thromboinflammatory properties against stroke

	Targeting the contact-kinin system: A cyclopeptide with anti-thromboinflammatory properties against stroke
	Wang, WT; Zhang, Y; Fang, YQ; Gao, JN; Thuku, RC; Yang, J; Na, C; Lu, QM; Fang, MQ
	2025
发表期刊	EUR J PHARMACOL
ISSN	0014-2999
卷号	998
摘要	The contact-kinin system plays a central role in the thromboinflammatory pathology of ischemic stroke. Modulating this pathway represents a promising strategy for the prevention and treatment of ischemic stroke. Based on our recent findings demonstrating that the short peptide SD6 (SLGASD), derived from a specific influenza-related immunoglobulin heavy chain junction region sequence, exhibits anti-coagulant properties, we designed a cyclized version, cycloSD6, and evaluated its anti-ischemic stroke potential. Notably, cycloSD6 showed enhanced inhibition of activated coagulation factor XII (FXIIa; with an inhibition constant (Ki) of 41.27 mu M) and plasma kallikrein (PKa; Ki: 28.54 mu M), two key enzymes in the contact-kinin system, surpassing the inhibitory effects of its linear form. In vitro, 4-100 mu M of CycloSD6 inhibited LPS-induced inflammation. And CycloSD6 at doses of 1 and 4 mg/kg displayed significant anti-thrombotic functions in several mouse models, including carrageenan-induced tail thrombosis, FeCl3-induced arterial thrombosis, and cortical photothrombosis models, and did not affect mouse tail bleeding time. The peptide also exerted comparable anti-ischemic stroke effects to those of ecallantide (DX-88), a kallikrein inhibitor approved for the treatment of hereditary angioedema, in a mouse model of transient middle cerebral artery occlusion. Thus, this short peptide CycloSD6, which dual targets FXII and PKa, harbors anti-thromboinflammation and anti-stroke properties with low bleeding risk. And these findings suggest that cycloSD6 may serve as a potential therapeutic candidate or template for the development of agents targeting ischemic stroke.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14606
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
推荐引用方式 GB/T 7714	Wang, WT,Zhang, Y,Fang, YQ,et al. Targeting the contact-kinin system: A cyclopeptide with anti-thromboinflammatory properties against stroke[J]. EUR J PHARMACOL,2025,998.
APA	Wang, WT.,Zhang, Y.,Fang, YQ.,Gao, JN.,Thuku, RC.,...&Fang, MQ.(2025).Targeting the contact-kinin system: A cyclopeptide with anti-thromboinflammatory properties against stroke.EUR J PHARMACOL,998.
MLA	Wang, WT,et al."Targeting the contact-kinin system: A cyclopeptide with anti-thromboinflammatory properties against stroke".EUR J PHARMACOL 998(2025).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
LR2025041013.pdf（7927KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文