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Updated: Nov 29, 2025

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
Chemical Modification of Linkers Provides Stable Linker-Payloads for the Generation of Antibody-Drug Conjugates
Yam B Poudel1, Naidu S Chowdari1, Heng Cheng1
1Bristol-Myers Squibb Research & Development, 700 Bay Road, Redwood City, California 94063, United States.
Abstract:
Stability of antibody-drug conjugates (ADCs) in mouse serum is one of the critical requirements for the evaluation of ADCs in mouse tumor models. Described herein is a strategy to address the mouse serum instability of uncialamycin linker-payloads through various chemical approaches that involve modification of different parts of the linker and payload. This effort ultimately led to the identification of a m-amide p-aminobenzyl carbamate (MA-PABC) group that resulted in linkers with dramatic improvement of mouse serum stability without affecting the desired proteolytic cleavage.
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