ArticleCell chemical biology2021
Systematic Activity Maturation of a Single-Domain Antibody with Non-canonical Amino Acids through Chemical Mutagenesis.
Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment.Frontiers in immunology · 2021Pooled it
- Targeted inhibition of M2 macrophages polarization via a PDC attenuates chronic pancreatitis through the PPARα pathway.iScience · 2026Article
- Kinetic Resolution of Epimeric Proteins Enables Stereoselective Chemical Mutagenesis.Journal of the American Chemical Society · 2024Article
- Chemo- and regio-selective differential modification of native cysteines on an antibodyChemical science · 2024Article
- Article
- Sequence-based prediction of the intrinsic solubility of peptides containing non-natural amino acids.Nature communications · 2023Article
- Overexpression of recombinant proteins containing non-canonical amino acids in Vibrio natriegens: p-azido-L-phenylalanine as coupling site forAmino acids · 2022Article
- A Chemical Mutagenesis Approach to Insert Post-translational Modifications in Aggregation-Prone Proteins.ACS chemical neuroscience · 2022Article
- Research progress on unique paratope structure, antigen binding modes, and systematic mutagenesis strategies of single-domain antibodies.Frontiers in immunology · 2022Review
- Computational maturation of a single-domain antibody against Aβ42 aggregation.Chemical science · 2021Article
- Dichloro Butenediamides as Irreversible Site-Selective Protein Conjugation Reagent.Angewandte Chemie (International ed. in English) · 2021Article
- Chemical Diversification of Simple Synthetic Antibodies.ACS chemical biology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Great advances have been made over the last four decades in therapeutic and diagnostic applications of antibodies. The activity maturation of antibody candidates, however, remains a significant challenge. To address this problem, we present a method that enables the systematic enhancement of the activity of a single-domain antibody through the post-translational installation of non-canonical side chains by chemical mutagenesis. We illustrate this approach by performing a structure-activity relationship study beyond the 20 naturally occurring amino acids on a single-domain antibody designed in silico to inhibit the aggregation of the amyloid-β peptide, a process closely linked to Alzheimer's disease. We found that this approach can improve, by five orders of magnitude, the anti-aggregation activity of the starting single-domain antibody, without affecting its stability. These results show that the expansion of the chemical space available to antibodies through chemical mutagenesis can be exploited for the systematic enhancement of the activity of these molecules.
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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.