Department of Pharmaceutical Chemistry , University of Kansas , 2095 Constant Avenue , Lawrence , Kansas 66047 , United States.
Department of Chemistry , University of Kansas , 1251 Wescoe Hall Drive , Lawrence , Kansas 66047 , United States.
Bioconjug Chem. 2018 Mar 21;29(3):686-701. doi: 10.1021/acs.bioconjchem.7b00633. Epub 2018 Feb 1.
Interrogating biological systems is often limited by access to biological probes. The emergence of "click chemistry" has revolutionized bioconjugate chemistry by providing facile reaction conditions amenable to both biologic molecules and small molecule probes such as fluorophores, toxins, or therapeutics. One particularly popular version is the copper-catalyzed azide-alkyne cycloaddition (AAC) reaction, which has spawned new alternatives such as the strain-promoted azide-alkyne cycloaddition reaction, among others. This focused review highlights practical approaches to AAC reactions for the synthesis of peptide or protein bioconjugates and contrasts current challenges and limitations in light of recent advances in the field. The conical success of antibody drug conjugates has expanded the toolbox of linkers and payloads to facilitate practical applications of bioconjugation to create novel therapeutics and biologic probes. The AAC reaction in particular is poised to enable a large set of functionalized molecules as a combinatorial approach to high-throughput bioconjugate generation, screening, and honing of lead compounds.
研究生物系统通常受到生物探针获取的限制。“点击化学”的出现通过提供适用于生物分子和小分子探针（如荧光团、毒素或治疗剂）的简便反应条件，彻底改变了生物缀合化学。一种特别流行的版本是铜催化的叠氮-炔环加成（AAC）反应，它催生了应变促进的叠氮-炔环加成反应等新的替代品。本综述重点介绍了用于合成肽或蛋白质生物缀合物的 AAC 反应的实用方法，并根据该领域的最新进展，对比了当前的挑战和局限性。抗体药物偶联物的成功应用拓展了连接子和有效载荷的工具包，以促进生物缀合在创造新型治疗剂和生物探针方面的实际应用。特别是 AAC 反应有望使一系列功能化分子成为高通量生物缀合生成、筛选和先导化合物优化的组合方法。
