Assembly of pH-Responsive Antibody-Drug-Inspired Conjugates

文献类型： 外文期刊

第一作者： Raabe, Marco

作者： Raabe, Marco;Heck, Astrid Johanna;Fuehrer, Siska;Schauenburg, Dominik;Pieszka, Michaela;Zegota, Maksymilian Marek;Nuhn, Lutz;Ng, David Y. W.;Kuan, Seah Ling;Weil, Tanja;Raabe, Marco;Pieszka, Michaela;Wang, Tao;Zegota, Maksymilian Marek;Kuan, Seah Ling;Weil, Tanja;Raabe, Marco;Wang, Tao

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关键词： antibody-inspired conjugates; avidin-biotin; boronic acid-salicylhydroxamate; pH-responsive linkers; protein-drug conjugates

期刊名称：MACROMOLECULAR BIOSCIENCE （ 影响因子：5.859； 五年影响因子：4.752 ）

ISSN： 1616-5187

年卷期： 2022 年 22 卷 2 期

页码：

收录情况： SCI

摘要： With the advent of chemical strategies that allow the design of smart bioconjugates, peptide- and protein-drug conjugates are emerging as highly efficient therapeutics to overcome limitations of conventional treatment, as exemplified by antibody-drug conjugates (ADCs). While targeting peptides serve similar roles as antibodies to recognize overexpressed receptors on diseased cell surfaces, peptide-drug conjugates suffer from poor stability and bioavailability due to their low molecular weights. Through a combination of a supramolecular protein-based assembly platform and a pH-responsive linker, the authors devise herein the convenient assembly of a trivalent protein-drug conjugate. The conjugate should ideally possess distinct features of ADCs such as 1) recognition sites that recognize cell receptor and are arranged on 2) distinct locations on a high molecular weight protein scaffold, 3) a stimuli-responsive linker, as well as 4) an attached payload such as a drug molecule. These AD-like conjugates target cancer cells that overexpress somatostatin receptors, can enable controlled release in the microenvironment of cancer cells through a new pH-responsive biotin linker, and exhibit stability in biological media.

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