A Picomolar MBP-Binding Nanobody for Target Enrichment and Modular Complex Engineering

IF 3.5 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Bio & Med Chem Au Pub Date : 2026-08-19 Epub Date: 2026-07-06 DOI:10.1021/acsbiomedchemau.6c00053

Monica Chinellato, Elisa Franzin, Filippo Vascon, Paul-Albert Koenig, Florian I. Schmidt, Patrizia Pontisso, Laura Cendron

{"title":"A Picomolar MBP-Binding Nanobody for Target Enrichment and Modular Complex Engineering","authors":"Monica Chinellato, Elisa Franzin, Filippo Vascon, Paul-Albert Koenig, Florian I. Schmidt, Patrizia Pontisso, Laura Cendron","doi":"10.1021/acsbiomedchemau.6c00053","DOIUrl":null,"url":null,"abstract":"<p>The variable domains of heavy chain only antibodies,\r\nalso called\r\nnanobodies, have provided powerful new tools for biomedical research.\r\nTheir rapid development across multiple fields has helped address\r\nemerging scientific and clinical challenges, establishing single-domain\r\nantibodies (sdAbs) as highly adaptable platforms for a wide range\r\nof biotechnological and therapeutic applications. In this study, we\r\nidentified a nanobody from an alpaca immune library, sdAbCM1, that\r\nbinds to the maltose-maltodextrin binding protein, MBP, with picomolar\r\naffinity. Biophysical investigations showed that sdAbCM1 recognizes\r\na yet unreported epitope and interacts with MBP in its closed conformation\r\nwhen maltose is present. The high affinity, epitope specificity, and\r\nability to tolerate the ligand-bound state render sdAbCM1 a valuable\r\nand versatile biotechnological tool with potential applications such\r\nas detection, localization, and purification of MBP fusion proteins\r\nand protein complex engineering for single-particle microscopy.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 4","pages":"323–328"},"PeriodicalIF":3.5000,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Bio & Med Chem Au","FirstCategoryId":"1085","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsbiomedchemau.6c00053","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/7/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The variable domains of heavy chain only antibodies, also called nanobodies, have provided powerful new tools for biomedical research. Their rapid development across multiple fields has helped address emerging scientific and clinical challenges, establishing single-domain antibodies (sdAbs) as highly adaptable platforms for a wide range of biotechnological and therapeutic applications. In this study, we identified a nanobody from an alpaca immune library, sdAbCM1, that binds to the maltose-maltodextrin binding protein, MBP, with picomolar affinity. Biophysical investigations showed that sdAbCM1 recognizes a yet unreported epitope and interacts with MBP in its closed conformation when maltose is present. The high affinity, epitope specificity, and ability to tolerate the ligand-bound state render sdAbCM1 a valuable and versatile biotechnological tool with potential applications such as detection, localization, and purification of MBP fusion proteins and protein complex engineering for single-particle microscopy.

查看原文本刊更多论文

一种用于目标富集和模块化复杂工程的皮摩尔mbp结合纳米体

仅重链抗体的可变结构域，也称为纳米体，为生物医学研究提供了强大的新工具。它们在多个领域的快速发展帮助解决了新兴的科学和临床挑战，建立了单域抗体（sabs）作为广泛的生物技术和治疗应用的高度适应性平台。在这项研究中，我们从羊驼免疫文库中鉴定了一个纳米体sdAbCM1，它与麦芽糖-麦芽糖糊精结合蛋白MBP结合，具有微分子亲和力。生物物理研究表明，当麦芽糖存在时，sdAbCM1识别一个尚未报道的表位，并在其封闭构象中与MBP相互作用。高亲和力、表位特异性和耐受配体结合状态的能力使sdAbCM1成为一个有价值的、通用的生物技术工具，具有潜在的应用，如检测、定位和纯化MBP融合蛋白和单粒子显微镜下的蛋白质复合物工程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Bio & Med Chem Au 药物、生物、化学-

CiteScore

4.10

自引率

0.00%

发文量

期刊介绍： ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.