Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 38, 1090 Vienna, Austria.
Chair of Medicinal and Bioinorganic Chemistry, Department of Chemistry, Technical University of Munich, Lichtenbergstrasse 4, 85748 Garching, Germany.
Bioconjug Chem. 2020 May 20;31(5):1279-1288. doi: 10.1021/acs.bioconjchem.0c00152. Epub 2020 Apr 14.
The conjugation of metal-based scaffolds to peptides, proteins, or antibodies allows the systemic targeting of these payloads to specific locations in the body, such as target cells/tissues (e.g., cancer) and subcellular compartments, for either therapy or imaging. This Topical Review includes an overview of the available chemical strategies to achieve metal-peptidic bioconjugates for biomedical applications, focusing on the types of chemical functionalities used to tether the drug to the peptide directly or indirectly. Central to all the possible approaches is the development of highly efficient and selective bioconjugation reactions that operate under mild, peptide-compatible conditions. For each strategy, selected examples are highlighted with particular emphasis to the studies reporting the therapeutic effects of the metal-peptidic conjugates in the treatment of cancer. Overall, some of the herewith discussed cases clearly hold promise for translation into clinically meaningful applications in the field of targeted therapeutics. Nevertheless, novel chemical approaches enabling the chemoselective metalation of specific residues in peptides under biologically friendly conditions, as well as the design of stimuli-responsive bioconjugates, are still expected to emerge. Certainly, the peculiar biorthogonal reactivity of metallodrugs provides an enlarged toolbox of opportunities for bioconjugation. Therefore, we outline a number of possible future directions and applications.
将金属支架与肽、蛋白质或抗体结合，可使这些有效载荷靶向递送到体内的特定部位，如靶细胞/组织（如癌症）和亚细胞区室，用于治疗或成像。本专题评论包括概述用于生物医学应用的金属肽生物缀合物的现有化学策略，重点介绍用于将药物直接或间接连接到肽的化学官能团的类型。所有可能方法的核心是开发高效和选择性的生物缀合反应，这些反应在温和的、与肽相容的条件下进行。对于每种策略，都选择了一些具有代表性的例子，特别强调了报告金属肽缀合物在癌症治疗中治疗效果的研究。总的来说，这里讨论的一些案例显然有希望转化为靶向治疗领域具有临床意义的应用。然而，仍需要新的化学方法来实现肽中特定残基在生物友好条件下的化学选择性金属化，以及设计刺激响应性生物缀合物。当然，金属药物的特殊生物正交反应性为生物缀合提供了更大的机会工具箱。因此，我们概述了一些可能的未来方向和应用。
