I-Corps: An efficient enzymatic synthesis method for biomanufacturing of nucleoside analogues

University Of Maryland, College Park, College Park MD

Investigators

Abstract

Nucleoside mimics and their conjugates (referred to as nucleoside analogues or "NAs") have diverse applications ranging from anti-viral and anti-tumor agents to nutritional supplements. Current chemical approaches for the synthesis of NAs are time consuming, expensive, and inefficient. Recently, researchers developed an enzyme-assisted biochemical synthesis of NAs in high yield and in a one-pot, single step reaction. The goals of the I-Corps proposal are to develop this into a robust biomanufacturing process and explore the chemical diversity of NAs that can be synthesized using this enzymatic approach. Researchers envision the enzymatic aqueous-based synthesis of NAs as the core technology for the manufacture of NAs that is inexpensive, rapid, highly efficient, and stereo selective. The process would also be an environmentally-friendly alternative to the currently available chemical approaches which generate large quantities of chemical waste. Current chemical synthesis methods to make NAs are multi step, time consuming and generate significant chemical waste. This limits the scope of research and development of NAs as potential therapeutic agents, diagnostic tools, biochemical probes, and nutritional supplements. Using enzymatic reaction in aqueous base will produce no waste and thus help the environment. The adoptability of the proposed method for high-throughput screening of the chemical space of the small molecules that can be conjugated to the NAs greatly enhances the search for highly effective NAs. NAs are used in the treatment of global epidemics such as HIV and HCV. There is an unmet need to produce anti-viral drugs at a cheaper price to cater to the third world countries. By using cost effective enzymatic synthesis of NAs, one can imagine mass production of these drugs at affordable prices.