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AJICAP-M: Traceless Affinity Peptide Mediated Conjugation Technology for Site-Selective Antibody–Drug Conjugate Synthesis

Yutaka Matsuda, Natsuki Shikida, Noriko Hatada, Kei Yamada, Takuya Seki, Yuichi Nakahara, Yuta Endo, Kazutaka Shimbo, Kazutoshi Takahashi, Akira Nakayama, Brian A. Mendelsohn, Tomohiro Fujii, Tatsuya Okuzumi, Shigeo Hirasawa

2024Organic Letters26 citationsDOI

Abstract

A traceless site-selective conjugation method, "AJICAP-M", was developed for native antibodies at sites using Fc-affinity peptides, focusing on Lys248 or Lys288. It produces antibody-drug conjugates (ADCs) with consistent drug-to-antibody ratios, enhanced stability, and simplified manufacturing. Comparative in vivo assessment demonstrated AJICAP-M's superior stability over traditional ADCs. This technology has been successfully applied to continuous-flow manufacturing, marking the first achievement in site-selective ADC production. This manuscript outlines AJICAP-M's methodology and its effectiveness in ADC production.

Topics & Concepts

ConjugateChemistryCombinatorial chemistryAntibody-drug conjugatePeptideDrugAntibodyStereochemistryBiochemistryMonoclonal antibodyPharmacologyImmunologyMathematical analysisMedicineMathematicsBiologyMonoclonal and Polyclonal Antibodies ResearchChemical Synthesis and AnalysisHER2/EGFR in Cancer Research
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