Inhibition of platelet adhesion to exposed subendothelial collagen by steric hindrance with blocking peptide nanoparticles,Colloids and Surfaces B: Biointerfaces

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Inhibition of platelet adhesion to exposed subendothelial collagen by steric hindrance with blocking peptide nanoparticles
Colloids and Surfaces B: Biointerfaces ( IF 5.4 ) Pub Date : 2024-03-20 , DOI: 10.1016/j.colsurfb.2024.113866
Anqi Wang ₁ , Kai Yue ₂ , Xiaotong Yan ₁ , Weishen Zhong ₁ , Genpei Zhang ₁ , Lei Wang ₃ , Hua Zhang ₄ , Xinxin Zhang ₂

Affiliation

The inhibition of platelet adhesion to collagen in exposed vessels represents an innovative approach to the treatment of atherosclerosis and thrombosis. This study aimed to engineer peptide-based nanoparticles that prevent platelet binding to subendothelial collagen by engaging with collagen with high affinity. We examined the interactions between integrin α2/ glycoprotein VI/ von Willebrand factor A3 domain and collagen, as well as between the synthesized peptide nanoparticles and collagen, utilizing molecular dynamics simulations and empirical assays. Our findings indicated that the bond between von Willebrand factor and collagen was more robust. Specifically, the sequences SITTIDV, VDVMQRE, and YLTSEMH in von Willebrand factor were identified as essential for its attachment to collagen. Based on these sequences, three peptide nanoparticles were synthesized (BPa: Capric-GNNQQNYK-SITTIDV, BPb: Capric-GNNQQNYK-VDVMQRE, BPc: Capric-GNNQQNYK-YLTSEMH), each displaying significant affinity towards collagen. Of these, the BPa nanoparticles exhibited the most potent interaction with collagen, leading to a 75% reduction in platelet adhesion.

中文翻译：

通过封闭肽纳米粒子的空间位阻抑制血小板与暴露的内皮下胶原蛋白的粘附

抑制暴露血管中血小板与胶原蛋白的粘附代表了治疗动脉粥样硬化和血栓形成的创新方法。这项研究旨在设计基于肽的纳米粒子，通过与胶原蛋白高亲和力结合来防止血小板与内皮下胶原蛋白结合。我们利用分子动力学模拟和经验分析，研究了整合素 α2/糖蛋白 VI/血管性血友病因子 A3 结构域和胶原蛋白之间的相互作用，以及合成的肽纳米颗粒和胶原蛋白之间的相互作用。我们的研究结果表明，血管性血友病因子和胶原蛋白之间的结合更加牢固。具体而言，冯维勒布兰德因子中的序列 SITTIDV、VDVMQRE 和 YLTSEMH 被确定为其与胶原蛋白的附着所必需。基于这些序列，合成了三种肽纳米颗粒（BPa：Capric-GNNQQNYK-SITTIDV、BPb：Capric-GNNQQNYK-VDVMQRE、BPc：Capric-GNNQQNYK-YLTSEMH），每种都对胶原蛋白表现出显着的亲和力。其中，BPa 纳米粒子表现出与胶原蛋白最有效的相互作用，导致血小板粘附减少 75%。

更新日期：2024-03-20

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