Monobody是一种通过筛选技术获得的小分子工程蛋白质，首先由芝加哥大学（现于纽约大学朗格尼医学中心）的Shohei Koide博士提出并发明。 Monobody是基于 三型纤连蛋白结构域 （Fibronectin Type III, FN3）进行筛选和开发的，其大小只有10KDa左右，与传统的抗体相比，Monobody缺少二硫键以及相对小的分子量使其可以在还原性条件下的细胞质中折叠成正确的构象并稳定地存在。 因此，Monobody这类小分子药物较好地弥补了前文提到的目前靶向技术的 …

Monobodies are synthetic binding proteins constructed using a fibronectin type III domain (FN3) as a molecular scaffold. Specifically, this class of binding proteins are built upon a diversified library of the 10th FN3 domain of human fibronectin. Monobodies are a simple and robust alternative to antibodies for creating target-binding proteins.

We diversified positions on a β-sheet and surface loops that together form a concave surface. The new library produced binding proteins (termed “monobodies”) to multiple target proteins, generally with similar efficacy as the original, loop-focused library.

Genetically encoded monobodies are effective “tool biologics” for validating intracellular targets. They promote crystallization and help reveal the atomic structures of the monobody-target interface, which can inform drug design.

Monobodies lack disulfide bonds and thus they are particularly suited as genetically encoded reagents to be used intracellularly. This article reviews recent monobody-enabled studies that reveal new structures, molecular mechanisms and potential therapeutic opportunities.

2020年8月13日 · Monobodies are synthetic non-immunoglobulin customizable protein binders invaluable to basic and applied research, and of considerable potential as future therapeutics and diagnostic tools.

Monobodies are synthetic binding proteins that are constructed using a fibronectin type III domain (FN3) as a molecular scaffold. Monobodies are simple and robust alternative to antibodies in creating target-binding proteins. In 1998, we published the first paper demonstrating the monobody concept using the tenth FN3 domain of human fibronectin.

2023年10月9日 · In this study, we designed and synthesized a novel monobody variant with two cysteine substitutions that facilitate the synthetic process via sequential native chemical ligations and improve protein stability by disulfide bond formation.

2017年3月1日 · The difference between the natural PPI and a synthetic PPI is even more dramatic in the case of H-RAS. Monobody NS1 binds to a homodimerization interface of H-RAS [Fig. 4(D)]. H-RAS uses primarily two α-helices for dimerization. In contrast, the Monobody uses a β-sheet and loops.

研究人员通过monobody合成技术合成了一种 单克隆抗体 12VC1，能够识别激活状态的KRAS（G12V）和KRAS（G12C），对 野生型 KRAS的选择性高达400倍。晶体结构表明，12VC1通过一个浅口袋识别突变，与Ras-effector的相互作用竞争。

2016年11月14日 · Monobody本质上是类似抗体的合成结合蛋白，根据设计以及结构上的不同，能够和酶、受体等许多蛋白质结合。Monobody发挥作用不依赖于环境，可以被当做是蛋白质版的抑制剂。

2022年10月11日 · Here, the authors improve the targeting efficiency of antibodies on nanoparticles using a monobody adapter to correctly orientate the antibody to preserve targeting function and demonstrate ...

Genetically encoded monobodies are effective “tool biologics” for validating intracellular targets. They promote crystallization and help reveal the atomic structures of the monobody-target interface, which can inform drug design.

2019年4月26日 · Monobodies are small engineered binding proteins that, upon expression in cells, can inhibit signaling of cytosolic oncoproteins with outstanding selectivity. Efficacy may be further increased by inducing degradation of monobody targets through fusion to the von Hippel–Lindau (VHL) substrate receptor of the Cullin2-E3 ubiquitin ligase complex.

Among synthetic binding protein platforms, the most established systems include Affibodies, Anticalins, Monobodies and DARPins [Fig. 1 (B)]. Affibodies are based on the Z domain of protein A from Staphylococcus aureus.

2020年2月1日 · Monobodies lack disulfide bonds and thus they are particularly suited as genetically encoded reagents to be used intracellularly. This article reviews recent monobody-enabled studies that reveal new structures, molecular mechanisms and …

Up to now, targeted cancer therapeutics come in two main flavours: therapeutic monoclonal antibodies (mAbs) target the extracellular side of cell surface receptor proteins on tumour cells or on cells in the tumour microenvironment, whereas small-molecule chemical inhibitors of protein kinases and a few other enzymes (e.g., the proteasome, poly A...

2020年8月13日 · Monobodies are synthetic non-immunoglobulin customizable protein binders invaluable to basic and applied research, and of considerable potential as future therapeutics and diagnostic tools.

2015年2月4日 · Monobodies have been engineered to bind a wide variety of target proteins with high affinity and specificity. Using alanine-scanning mutagenesis simulations, we identified two scaffold residues that are critical to the binding interaction between the monobody YS1 and its ligand, maltose-binding protein (MBP).