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基于自组装纳米粒子文库筛选中和蜂毒素溶血毒性的亲和配体。

Selection of Affinity Reagents to Neutralize the Hemolytic Toxicity of Melittin Based on a Self-Assembled Nanoparticle Library.

机构信息

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.

出版信息

ACS Appl Mater Interfaces. 2020 Apr 8;12(14):16040-16049. doi: 10.1021/acsami.0c00303. Epub 2020 Mar 26.

DOI:10.1021/acsami.0c00303
PMID:32174109
Abstract

Antibodies are the most common affinity reagents for specific target recognition. However, their applications are limited by high cost and low stability. Thus, seeking substitutes for antibodies is of great significance. In this work, we designed a library containing 82 self-assembled nanoparticles (SNPs) based on the self-assembly of β-cyclodextrin polymers and adamantane derivatives, and then screened out eight types of SNPs capable of suppressing the toxicity of melittin using a hemolytic activity neutralization assay. The affinities of the SNPs to melittin were demonstrated using surface plasmon resonance (SPR). As evidenced by cytotoxicity experiments, SNPs could also suppress the toxicity of melittin to other cells. In addition, to verify the universality of our method, 11 types of SNPs capable of neutralizing another toxic peptide, phenolic soluble polypeptide (PSMα3) secreted by , were selected from the same SNP library. Our self-assembly-based method for the library preparation has the advantages of flexible design, mild experimental condition, and simple operation, which is expected to seek artificial affinity reagents for more species.

摘要

抗体是最常见的用于特异性靶标识别的亲和试剂。然而,由于成本高和稳定性低,它们的应用受到限制。因此,寻找抗体的替代品具有重要意义。在这项工作中,我们设计了一个包含 82 个自组装纳米颗粒(SNPs)的文库,该文库基于β-环糊精聚合物和金刚烷衍生物的自组装,然后使用溶血活性中和测定法筛选出 8 种能够抑制蜂毒素毒性的 SNPs。使用表面等离子体共振(SPR)证明了 SNPs 与蜂毒素的亲和力。细胞毒性实验表明,SNP 还可以抑制蜂毒素对其他细胞的毒性。此外,为了验证我们方法的通用性,从相同的 SNP 文库中选择了 11 种能够中和另一种由 分泌的有毒肽,即酚溶性多肽(PSMα3)的 SNP。我们基于自组装的文库制备方法具有设计灵活、实验条件温和、操作简单等优点,有望为更多物种寻找人工亲和试剂。

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