Click Chemistry Conjugations

Area of Science:

• Bioconjugation Chemistry
• Medicinal Chemistry
• Antibody-Drug Conjugate Development

Background:

• Click chemistry offers precise control over biomolecule modification.
• Chemically defined antibody-drug conjugates (ADCs) offer advantages in homogeneity and site-specificity.
• Recent years have seen increased application of click chemistry in ADC synthesis.

Purpose of the Study:

• To provide a historical overview of click chemistry in ADCs.
• To enumerate various click chemistries used for ADC synthesis.
• To describe protocols for common ADC conjugation methods.

Main Methods:

• Review of literature on click chemistry applications in ADCs.
• Enumeration of click chemistries for ADC synthesis, including clinical candidates.
• Detailed protocols for carbonyl-aminooxy coupling and strain-promoted azide-alkyne cycloaddition.

Main Results:

• Demonstrated benefits of homogeneity and site-specificity in ADCs through click chemistry.
• Identification of multiple click chemistry strategies for ADC development.
• Practical protocols for synthesizing ADCs using specific click reactions.

Conclusions:

• Click chemistry is a powerful tool for creating defined ADCs.
• The described methods facilitate the synthesis of homogeneous ADCs.
• Further clinical investigation of click chemistry-based ADCs is warranted.