ArticleBioorganic & medicinal chemistry2020
An optimal "Click" formulation strategy for antibody-drug conjugate synthesis.
Article in Bioorganic & medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Chemotherapeutic Drug-Antibody Conjugates (ChemoBodies): Recent Advances and Future Directions.Current oncology reports · 2025Review
- Copper-catalysed azide-alkyne cycloaddition on live M13 bacteriophage for expanding the molecular diversity of phage-displayed peptide libraries.RSC chemical biology · 2025Article
- Signature of click chemistry in advanced techniques for cancer therapeutics.RSC advances · 2025Review
- Click Chemistry-Based Bioconjugation of Iron Oxide Nanoparticles.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Chemical Tagging of Bioactive Amides by Cooperative Catalysis: Applications in the Syntheses of Drug Conjugates.Journal of the American Chemical Society · 2023Article
- Synthesis and Application of Two-Photon Active Fluorescent Rhodol Dyes for Antibody Conjugation andACS omega · 2023Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
As a versatile reaction for bioconjugation, Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) has enormous potential in the synthesis of antibody-drug conjugates (ADCs). In order to optimize CuAAC-based ADC synthesis, we characterized kinetically different formulation processes by mimicking ADC synthesis using small molecules and subsequently revealed unique kinetic behaviors of different combinations of alkyne and azide conditions. Our results indicate that under ADC synthesis conditions, for an alkyne-containing drug, its concentration has minimal impact on the reaction rate when an antibody has a non-metal-chelating azide but is proportional to concentration when an antibody contains a metal-chelating azide; however, for an alkyne-containing antibody, the ADC synthesis rate is proportional to the concentration of a drug with a non-metal-chelating azide but displays almost no dependence on drug concentration with a metal-chelating azide. Based on our results, we designed and tested an optimal "click" formulation strategy that allowed rapid and cost-effective synthesis of a new ADC.
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Registered trials
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