64 | December 2021 www.facs.website Katsunori Tanaka Katsunori Tanaka received his B.S degree (1996) and Ph.D. degree (2002) in chemistry from Kwansei Gakuin University under the guidance of Prof. Shigeo Katsumura. Following a postdoctoral stint with Prof. Koji Nakanishi at Columbia University, he worked as an assistant professor in the group of Prof. Koichi Fukase at Osaka University. At present, he holds concurrent roles as a professor at the Tokyo Institute of Technology and as a Chief Scientist at the RIKEN institute. In addition, he also holds various adjunct positions; one being as a Professor at Kazan Federal University. His research interests include organic synthesis, molecular imaging, in vivo synthesis, and natural products. Tsung-Che Chang Tsung-Che Chang received his Ph.D. degree (2012) in chemistry from National Tsing-Hua University under the direction of Prof. Chun-Cheng Lin. Following a JSPS postdoctoral fellowship with Prof. Koichi Fukase at Osaka University, he worked as a postdoctoral researcher in the group of Katsunori Tanaka at the RIKEN institute. His research interests are in the field of carbohydrate chemistry and biocatalysis. Therapeutic in vivo synthetic chemistry by glycosylated artificial metalloenzymes for innovative biomedical modality This article is to depict the steps taken by our team for the development of glycosylated artificial metalloenzymes (GArMs) that we have used to develop therapeutic in vivo synthetic chemistry. To achieve this goal, we have had to combine technologies developed over the course of a decade that range from protein conjugation methodologies, identification of glycan-dependent targeting, development of functional biocatalysis and the biocompatible reactions. As a result, we have begun to reveal the framework for GArM complexes and their potential towards creating novel biotechnological tools and therapeutic applications. Therapeutic In Vivo Synthetic Chemistry In the past century, synthetic chemistry, which is the artificial execution of various chemical reactions to obtain the desired products, has greatly enabled the development of pharmaceutical research, leading to an improvement in the health of patients worldwide. Recently, innovations in new synthetic methods, biocatalysis, reaction miniaturization, and chemoinformatics have powerfully improved the quality of products in pharmaceutical research. One of the most influential research trends within the last few decades was the race to discover anticancer drugs. However, the adverse health effects of current By Katsunori Tanaka and Tsung-Che Chang https://doi.org/10.51167/acm00025 anticancer drugs have sparked a new research trend centered on localized drug delivery to avoid unwanted side effects against untargeted normal cells. 1 Currently, numerous research groups are developing vastly different approaches to overcome this issue. Some notable approaches (Fig. 1A-D) include the use of external stimuli (ex/ MRI, ultrasound, and light)2, and bioorthogonal click-to-release chemistry3 to convert prodrugs into their active form. In addition, pH-sensing liposomes and nanoparticles have extensively explored to release encapsulated drugs under the acidic conditions of cancers4. Recently, abiotic
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