School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China.
School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China; Shunde Graduate School of University of Science and Technology Beijing, Shunde, Guangdong Province 528399, China.
Colloids Surf B Biointerfaces. 2024 May;237:113866. doi: 10.1016/j.colsurfb.2024.113866. Epub 2024 Mar 20.
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.
抑制暴露血管中的血小板黏附于胶原代表了一种治疗动脉粥样硬化和血栓形成的创新方法。本研究旨在设计基于肽的纳米颗粒，通过与胶原高亲和力结合来防止血小板与内皮下胶原结合。我们利用分子动力学模拟和经验性检测，研究了整合素 α2/糖蛋白 VI/血管性血友病因子 A3 结构域与胶原之间，以及合成肽纳米颗粒与胶原之间的相互作用。我们的研究结果表明，血管性血友病因子与胶原之间的结合更为牢固。具体而言，血管性血友病因子中序列 SITTIDV、VDVMQRE 和 YLTSEMH 被鉴定为其与胶原附着的必需序列。基于这些序列，我们合成了三种肽纳米颗粒（BPa：Capric-GNNQQNYK-SITTIDV、BPb：Capric-GNNQQNYK-VDVMQRE、BPc：Capric-GNNQQNYK-YLTSEMH），它们均显示出对胶原的显著亲和力。其中，BPa 纳米颗粒与胶原的相互作用最强，导致血小板黏附减少 75%。
