Guryanov I, Real-Fernández F, Sabatino G, Prisco N, Korzhikov-Vlakh V, Biondi B, Papini A M, Korzhikova-Vlakh E, Rovero P, Tennikova T
Institute of Chemistry, St. Petersburg State University, St. Petersburg, 198504, Russia.
Laboratory of Peptide and Protein Chemistry and Biology, Department of Chemistry "Ugo Schiff", University of Florence, 50019, Sesto Fiorentino, Italy.
J Pept Sci. 2019 Feb;25(2):e3142. doi: 10.1002/psc.3142.
The study of the process of HIV entry into the host cell and the creation of biomimetic nanosystems that are able to selectively bind viral particles and proteins is a high priority research area for the development of novel diagnostic tools and treatment of HIV infection. Recently, we described multilayer nanoparticles (nanotraps) with heparin surface and cationic peptides comprising the N-terminal tail (Nt) and the second extracellular loop (ECL2) of CCR5 receptor, which could bind with high affinity some inflammatory chemokines, in particular, Rantes. Because of the similarity of the binding determinants in CCR5 structure, both for chemokines and gp120 HIV protein, here we expand this approach to the study of the interactions of these biomimetic nanosystems and their components with the peptide representing the V3 loop of the activated form of gp120. According to surface plasmon resonance results, a conformational rearrangement is involved in the process of V3 and CCR5 fragments binding. As in the case of Rantes, ECL2 peptide showed much higher affinity to V3 peptide than Nt (K = 3.72 × 10 and 1.10 × 10 M, respectively). Heparin-covered nanoparticles bearing CCR5 peptides effectively bound V3 as well. The presence of both heparin and the peptides in the structure of the nanotraps was shown to be crucial for the interaction with the V3 loop. Thus, short cationic peptides ECL2 and Nt proved to be excellent candidates for the design of CCR5 receptor mimetics.
研究HIV进入宿主细胞的过程以及创建能够选择性结合病毒颗粒和蛋白质的仿生纳米系统，是开发新型诊断工具和治疗HIV感染的高度优先研究领域。最近，我们描述了具有肝素表面和阳离子肽的多层纳米颗粒（纳米陷阱），这些阳离子肽包含CCR5受体的N末端尾巴（Nt）和第二个细胞外环（ECL2），它们可以与一些炎症趋化因子，特别是RANTES，以高亲和力结合。由于CCR5结构中趋化因子和HIV gp120蛋白的结合决定因素相似，在此我们将这种方法扩展到研究这些仿生纳米系统及其组件与代表活化形式gp120的V3环的肽之间的相互作用。根据表面等离子体共振结果，V3和CCR5片段结合过程涉及构象重排。与RANTES的情况一样，ECL2肽对V3肽的亲和力远高于Nt（K分别为3.72×10和1.10×10 M）。带有CCR5肽的肝素覆盖纳米颗粒也能有效结合V3。纳米陷阱结构中肝素和肽的存在对于与V3环的相互作用至关重要。因此，短阳离子肽ECL2和Nt被证明是设计CCR5受体模拟物的优秀候选物。
