Applications of Bioorthogonal Chemistry in Tumor-Targeted Drug Discovery

• Published in: Current topics in medicinal chemistry Vol. 19; no. 11; p. 892
• Main Authors: Liu, Gang, Wold, Eric A, Zhou, Jia
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-01-2019
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Proliferation - drug effects; Drug Discovery; Humans; Molecular Structure; Neoplasms - drug therapy; Neoplasms - pathology; Chemical reactions; Protein activation; Tumor-targeted drug discovery; Bifunctional molecules; Bioorthogonal Chemistry
• ISSN: 1873-4294
• DOI: 10.2174/1568026619666190510091921

Chemical reactions that can proceed in living systems while not interfering with native biochemical processes are collectively referred to as bioorthogonal chemistry. Selectivity, efficiency, and aqueous compatibility are three significant characteristics of an ideal bioorthogonal reaction. To date, the specialized bioorthogonal reactions that have been reported include: Cu (I)-catalyzed [3 + 2] azido- alkyne cycloadditions (CuAAC), strain-promoted [3 + 2] azide-alkyne cycloadditions (SPAAC), Staudinger ligation, photo-click 1,3-dipolar cycloadditions, strain-promoted alkyne-nitrone cycloadditions (SPANC), transition metal catalysis (TMC), and inverse electron demand Diels-Alder (IEDDA). These reactions are divided into two subtypes, 1) bond-formation reactions (e.g. CuAAC, SPAAC, photo-click cycloadditions, SPANC), which can be conventionally applied in the chemical biology field for target identification, protein-specific modifications and others; and 2) bond-release reactions (e.g. Staudinger ligation, TMC, and IEDDA), which are emerging as powerful approaches for the study of protein activation and drug discovery. Over the past decade, bioorthogonal chemistry has enabled important compound design features in targeted drug discovery and has expanded biological knowledge on intractable targets. Research groups have also focused on the discovery of reactions with improved biocompatibility and increased reaction rates, which will undoubtably prove essential for future therapeutic development. Herein, we highlight two significant applications of bioorthogonal chemistry to drug discovery, which are tumor-targeted prodrug delivery and activation, and self-assembly of bifunctional molecules. The relevant challenges and opportunities are also discussed.