The design, synthesis, and evaluation of two universal doxorubicin-linkers: Preparation of conjugates that retain topoisomerase II activity

…, C Ballatore, R Castillo, AB Smith, AJ Castellino

Index: Sun, Chengzao; Aspland, Simon E.; Ballatore, Carlo; Castillo, Rosario; Smith III, Amos B.; Castellino, Angelo J. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 1 p. 104 - 107

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Citation Number: 12

Abstract

The design, synthesis, and evaluation of two N-alkylmaleimide aldehydes have been achieved, which upon reductive alkylation with the C3′-amino group of doxorubicin (DOX) permits the preparation of DOX conjugates via Michael addition of thiol-containing vectors. This method enables the mild, facile, and high-throughput preparation of DOX conjugates that retain the basic C3′-nitrogen, a pre-requisite for topoisomerase II inhibition. Seven ...