ArticleScientific reports2017
Rigidly connected multispecific artificial binders with adjustable geometries.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed.
- Docking of virtual libraries identifies small-molecule agonists of neurotensin receptors with analgesic activity.Nature communications · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Modular binder technology by NGS-aided, high-resolution selection in yeast of designed armadillo modules.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- SpyMask enables combinatorial assembly of bispecific binders.Nature communications · 2024Article
- A high throughput bispecific antibody discovery pipeline.Communications biology · 2023Article
- Engineering of a Bispecific Nanofitin with Immune Checkpoint Inhibitory Activity Conditioned by the Cross-Arm Binding to EGFR and PDL1.Biomolecules · 2023Article
- Enzymes in the time of COVID-19: An overview about the effects in the human body, enzyme market, and perspectives for new drugs.Medicinal research reviews · 2022Review
- Crystal structure of the αNature communications · 2022Article
- Generation of ordered protein assemblies using rigid three-body fusion.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism.Science advances · 2021Article
- Development of imaging scaffolds for cryo-electron microscopy.Current opinion in structural biology · 2020Review
- Elfin UI: A Graphical Interface for Protein Design With Modular Building Blocks.Frontiers in bioengineering and biotechnology · 2020Article
- Rigid fusions of designed helical repeat binding proteins efficiently protect a binding surface from crystal contacts.Scientific reports · 2019Article
- Structural analysis of biological targets by host:guest crystal lattice engineering.Scientific reports · 2019Article
- A 3.8 Å resolution cryo-EM structure of a small protein bound to an imaging scaffold.Nature communications · 2019Article
- Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Near-atomic cryo-EM imaging of a small protein displayed on a designed scaffolding system.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Design and applications of a clamp for Green Fluorescent Protein with picomolar affinity.Scientific reports · 2017Article
- Stability-Diversity Tradeoffs Impose Fundamental Constraints on Selection of Synthetic Human VFrontiers in immunology · 2017Article
- Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multivalent binding proteins can gain biological activities beyond what is inherent in the individual binders, by bringing together different target molecules, restricting their conformational flexibility or changing their subcellular localization. In this study, we demonstrate a method to build up rigid multivalent and multispecific scaffolds by exploiting the modular nature of a repeat protein scaffold and avoiding flexible linkers. We use DARPins (Designed Ankyrin Repeat Proteins), synthetic binding proteins based on the Ankyrin-repeat protein scaffold, as binding units. Their ease of in vitro selection, high production yield and stability make them ideal specificity-conferring building blocks for the design of more complex constructs. C- and N-terminal DARPin capping repeats were re-designed to be joined by a shared helix in such a way that rigid connector modules are formed. This allows us to join two or more DARPins in predefined geometries without compromising their binding affinities and specificities. Nine connector modules with distinct geometries were designed; for eight of these we were able to confirm the structure by X-ray crystallography, while only one did not crystallize. The bispecific constructs were all able to bind both target proteins simultaneously.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.