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高亲和力结合 SARS-CoV-2 刺突受体结合域的肽结合物。

Peptide Binder with High-Affinity for the SARS-CoV-2 Spike Receptor-Binding Domain.

机构信息

State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.

Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.

出版信息

ACS Appl Mater Interfaces. 2022 Jun 29;14(25):28527-28536. doi: 10.1021/acsami.2c03707. Epub 2022 Jun 17.

DOI:10.1021/acsami.2c03707
PMID:35713340
Abstract

Rapid antigen detection tests are urgently needed for the early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The discovery of a binder with high affinity and selectivity for the biomarkers presented by SARS-CoV-2 is crucial to the development of the rapid antigen detection method. We utilized the surface biopanning to identify a peptide binder R1 from a phage-displayed peptide library consisting of 10 independent phage recombinants. The R1 peptide exhibited high-affinity for specific binding with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with a dissociation constant of (7.5 ± 1.9) × 10 M, which maintained high binding affinity with the RBD derived from Gamma, Lambda, Delta, and Omicron variants. The composition and sequence dependence of binding characteristics in R1-RBD interactions was revealed by the binding affinity fluctuations between RBD and the scrambled sequences or single-site mutants of R1. The R1-functionalized gold nanoparticles possessed concentration-dependent response to RBD and selectivity over bovine serum albumin and human serum albumin. The peptide binder R1 shows the potential to be used for constructing a rapid detection method for the early-stage diagnostics for SARS-CoV-2.

摘要

快速抗原检测对于严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的早期诊断至关重要。发现与 SARS-CoV-2 呈现的生物标志物具有高亲和力和选择性的结合物对于快速抗原检测方法的发展至关重要。我们利用表面生物淘选从由 10 个独立噬菌体重组体组成的噬菌体展示肽文库中鉴定出一个肽结合物 R1。R1 肽与 SARS-CoV-2 刺突蛋白的受体结合域 (RBD) 具有高亲和力的特异性结合,解离常数为 (7.5 ± 1.9) × 10 M,与来自 Gamma、Lambda、Delta 和 Omicron 变体的 RBD 保持高结合亲和力。通过 RBD 与随机序列或 R1 的单点突变体之间的结合亲和力波动,揭示了 R1-RBD 相互作用中结合特性的组成和序列依赖性。R1 功能化的金纳米颗粒对 RBD 具有浓度依赖性响应,并且对牛血清白蛋白和人血清白蛋白具有选择性。肽结合物 R1 显示出用于构建 SARS-CoV-2 早期诊断快速检测方法的潜力。

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