2021 Fiscal Year Research-status Report

Application of gold-catalyzed hydroamination in sialic acids for the cancer-localized in vivo release of an immunotherapy drug

Research Project

Project/Area Number	21K05302
Research Institution	Institute of Physical and Chemical Research
Principal Investigator	張宗哲国立研究開発法人理化学研究所, 開拓研究本部, 特別研究員 (00774853)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	Prodrug / Gold metal / Immunotherapy
Outline of Annual Research Achievements	The aim of this proposal is to develop a cancer immunotherapy that unleashes an extremely active drug to targeted cancer cells in vivo for shut biosynthesis of sialic acids down, enabling immune cells to recognize and destroy the cancer cells. 3F-sialic acid is a highly active drug for the project, but it has no targeting, leading to cause side effects against normal cells. In the first year of the project, we have succeeded to prepared a 3F-sialic acid-based prodrug based on masking the C1 position of 3F-sialic acid by a biocompatible leaving via an unusual N-glycosylation. The prodrug can be activated by a gold catalyst in physiological condition in good yield. Hence, the prodrug could be used for localized drug release in vivo by a gold catalyst as a trigger in next step.
Current Status of Research Progress	Current Status of Research Progress 1: Research has progressed more than it was originally planned. Reason N-sialylation, could be a challenge step because only one simple N-sialylation with aniline was reported over the last 30 years. In this project, we have overcome the N-sialylation by a elegant and novel chemistry for preparation of 3F-sialic acid-based prodrug. So, the organic synthesis part of this project have been done. We use can the residue of the two years for solving biological part of the project.
Strategy for Future Research Activity	The next step will be to perform biological based studies. Initially, the various methods of glycoalbumin-Au catalyzed 3F-P-Neu5Ac release from the prodrug will be tested in cancer cell-based studies to determine the expression levels of sialic acids on cells surface
Causes of Carryover	In the next year, we would like to proceed many cell experiments for the project. So, we use the budget for paying biological cost.