Peptide Tag-nology for Preparation of Site-Specific Antibody-Drug Conjugates

Antibody-drug conjugates (ADC) are a rapidly growing therapeutic class that leverages the specificity of antibodies to deliver cytotoxic payloads to cells. While ADCs have demonstrated significant clinical success in cancer treatment, substantial challenges remain with regard to stability, low drug-antibody ratios, and heterogeneity that negatively impact pharmacokinetics, efficacy, and safety profiles. Bioconjugation and, in particular, peptide tag-nologies are key to overcoming these challenges and enabling future designs with diverse types of antibody formats, multiple payloads, and high drug loadings. This Viewpoint explores novel, facile peptide-based conjugation strategies to synthesize homogeneous and site-specific ADCs, describes the underlying conjugation reactions, and highlights the advantages of these technologies in comparison to classically used approaches.