多特异性抗gp120人工抗体的研制

IF 3.6 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-05-20 DOI:10.1002/cmdc.202500287
Yiwei Sun, Rui Ni, Yuan-Yuan Liu, Haifang Wang, Aoneng Cao
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引用次数: 0

摘要

广泛中和抗体是潜在的治疗药物,可以识别和阻止病毒的进入。但许多病毒,如人类免疫缺陷病毒(HIV),突变迅速,因此逃避治疗抗体。多特异性抗体及不同抗体组合可有效抑制免疫逃避。然而,许多障碍阻碍了多特异性抗体的发展,并且多种抗体联合的成本非常高。先前,我们证明了一类基于金纳米粒子(AuNP)的人工抗体,称为金体,可以通过简单地将抗体的互补决定区(cdr)嫁接到AuNP上而产生。在此,我们通过将CD4蛋白的HIV gp120结合片段和三种抗gp120抗体的CDR3环分别嫁接到aunp上,创建了四个单特异性抗gp120金体。值得注意的是,作为第一个概念验证研究,我们证明了四种不同的片段可以嫁接到同一个AuNP粒子上,从而创建了一种对gp120具有非常高结合亲和力的新型金体。原则上,这种新型金体的成本与单一单一金体相同,但它有可能成为多特定金体或多个金体的组合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Towards Multispecific Anti-Gp120 Artificial Antibody.

Broadly neutralizing antibodies are potential therapeutic drugs that can recognize and block viral entry. But many viruses, such as human immunodeficiency virus (HIV), mutate rapidly and thus evade therapeutic antibodies. Multispecific antibodies and combinations of different antibodies can effectively suppress immune evasion. However, many barriers hinder the development of multispecific antibodies, and the cost of combining multiple antibodies is very high. Previously, a class of gold nanoparticle (AuNP)-based artificial antibodies, called goldbodies, were created by simply grafting the complementary-determining regions of antibodies onto AuNPs. In this study, four monospecific anti-gp120 goldbodies are created by grafting the HIV gp120-binding fragment of the CD4 protein and the CDR3 loops of three anti-gp120 antibodies onto AuNPs, respectively. Remarkably, as a first proof of concept, the study shows that all four different fragments can be grafted onto the same AuNP particle, thus creating a new type of goldbody with a very high binding affinity for gp120. In principle, this new type of goldbody costs the same as a single monospecific goldbody, but it has the potential to serve as a multispecific goldbody or a combination of multiple goldbodies.

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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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