ArticleNature communications2022
Engineering an autonomous VH domain to modulate intracellular pathways and to interrogate the eIF4F complex.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 17 citations in OpenAlex.
- Development of a Chicken Immunoglobulin Heavy Chain Variable Region (VH) Single-Domain Antibody (sdAb) Against Calsequestrin (CSQ) and Its Application.Antibodies (Basel, Switzerland) · 2025Article
- Chemical Probes for Studying the Eukaryotic Translation Initiation Factor 4E (eIF4E)-Regulated Translatome in Cancer.ACS pharmacology & translational science · 2025Review
- Structural Modeling of Nanobodies: A Benchmark of State-of-the-Art Artificial Intelligence Programs.Molecules (Basel, Switzerland) · 2023Article
- N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma.European journal of medical research · 2023Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An attractive approach to target intracellular macromolecular interfaces and to model putative drug interactions is to design small high-affinity proteins. Variable domains of the immunoglobulin heavy chain (VH domains) are ideal miniproteins, but their development has been restricted by poor intracellular stability and expression. Here we show that an autonomous and disufhide-free VH domain is suitable for intracellular studies and use it to construct a high-diversity phage display library. Using this library and affinity maturation techniques we identify VH domains with picomolar affinity against eIF4E, a protein commonly hyper-activated in cancer. We demonstrate that these molecules interact with eIF4E at the eIF4G binding site via a distinct structural pose. Intracellular overexpression of these miniproteins reduce cellular proliferation and expression of malignancy-related proteins in cancer cell lines. The linkage of high-diversity in vitro libraries with an intracellularly expressible miniprotein scaffold will facilitate the discovery of VH domains suitable for intracellular applications.
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Registered trials
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