Alternating iterative exponential growth oligomers as a sequence-defined platform for hydrophilic antibody-drug conjugates.

Authors

Zihuan Fu, Heather D Maynard

Published in

Organic & biomolecular chemistry. Sep 14, 2026. Epub Sep 14, 2026.

Abstract

Antibody-drug conjugates (ADCs) are a powerful therapeutic modality capable of tissue-specific delivery of highly potent cytotoxic warheads. One of the key challenges of ADCs is their hydrophobicity. Conjugation of typically hydrophobic cytotoxins to an antibody alters its physicochemical properties, resulting in decreased stability and poor pharmacokinetics. Herein, we report the synthesis of alternating iterative exponential growth (IEG) oligomers bearing orthogonal functionalities that serve as a versatile platform for installing diverse hydrophilic moieties and cytotoxic payloads. Incorporation of hydrophilic groups can partially offset payload hydrophobicity, yielding ADCs with improved overall hydrophilicity.

PMID:
42733971
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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