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Click chemistry has found wide application in bioconjugation, enabling control over the site of modification in biomolecules. Demonstrations of this chemistry to construct chemically defined antibody-drug conjugates (ADCs) have increased in recent years, following studies that support benefits of homogeneity and site-specificity of drug placement on the antibody. In this chapter, a brief history of early applications of this chemistry in ADCs is presented. Examples of click chemistries that are utilized for ADC synthesis, including those currently undergoing clinical investigations, are enumerated. Protocols for two common conjugation methods based on carbonyl-aminooxy coupling and strain-promoted azide-alkyne cycloaddition are described.

Two different classes of fluorescent dyes were prepared as a turn off/on sensor system for aldehydes. Amino derivatives of a boron dipyrromethene (BDP) fluorophore and a xanthene-derived fluorophore (rosamine) were prepared. Model compounds of their product with an aldehyde were prepared using salicylaldehyde. Both amino boron dipyrromethene and rosamine derivatives are almost non-fluorescent in polar and apolar solvent. However, imine formation with salicylaldehyde on each fluorophore increases the fluorescence quantum yield by almost a factor of 10 (from 0.05 to 0.4). These fluorophores are therefore suitable candidates for development of fluorescence-based sensors for aldehydes., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.