A Plug-and-Play Approach for the De Novo Generation of Dually Functionalized Bispecifics.,Bioconjugate Chemistry

当前位置： X-MOL 学术 › Bioconjugate Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A Plug-and-Play Approach for the De Novo Generation of Dually Functionalized Bispecifics.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-02-24 , DOI: 10.1021/acs.bioconjchem.0c00002
Antoine Maruani ₁ , Peter A Szijj ₁ , Calise Bahou ₁ , João C F Nogueira ₁ , Stephen Caddick ₁ , James R Baker ₁ , Vijay Chudasama _{1,

2}

Affiliation

Diseases are multifactorial, with redundancies and synergies between various pathways. However, most of the antibody-based therapeutics on the market interact with only one target, thus limiting their efficacy. The targeting of multiple epitopes could improve the therapeutic index of treatment and counteract mechanisms of resistance. To this effect, a new class of therapeutics has emerged: bispecific antibodies. Bispecific formation using chemical methods is rare and low-yielding and/or requires a large excess of one of the two proteins to avoid homodimerization and heterogeneity. In order for chemically prepared bispecifics to deliver their full potential, high-yielding, modular, and reliable cross-linking technologies are required. Herein, we describe a novel approach not only for the rapid and high-yielding chemical generation of bispecific antibodies from native antibody fragments, but also for the site-specific dual functionalization of the resulting bioconjugates. Based on orthogonal clickable functional groups, this strategy enables the assembly of functionalized bispecifics with controlled loading in a modular and convergent manner.

中文翻译：

从头开始生成双重功能化双特征的即插即用方法。

疾病是多因素的，在各种途径之间具有冗余和协同作用。然而，市场上大多数基于抗体的治疗剂仅与一个靶标相互作用，从而限制了它们的功效。靶向多个表位可以改善治疗的治疗指数并抵消耐药性机制。为此，出现了一类新的疗法：双特异性抗体。使用化学方法的双特异性形成是罕见且低产率的，和/或需要大量过量的两种蛋白质之一以避免同二聚化和异质性。为了使化学制备的双特异性试剂发挥其全部潜能，需要高产率，模块化和可靠的交联技术。在这里我们描述了一种新颖的方法，不仅用于从天然抗体片段快速高产化学生成双特异性抗体，而且还用于产生的生物缀合物的位点特异性双重功能化。基于正交可点击的官能团，该策略能够以模块化和聚合的方式组装功能化的双特异性药物，并控制装载量。

更新日期：2020-03-03

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11