Uridine natural products: Challenging targets and inspiration for novel small molecule inhibitors
Name
nihms-1615957.pdf
Description
Accepted version
Size
1.66 MB
Format
Unknown
Checksum (MD5)
0f5f82e75e30e02389ee01433cd502fc
Author(s)
Arbour, Christine A
Imperiali, Barbara
Date Issued
2020
Journal
Bioorganic and Medicinal Chemistry
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
© 2020 Elsevier Ltd Nucleoside derivatives, in particular those featuring uridine, are familiar components of the nucleoside family of bioactive natural products. The structural complexity and biological activities of these compounds have inspired research from organic chemistry and chemical biology communities seeking to develop novel approaches to assemble the challenging molecular targets, to gain inspiration for enzyme inhibitor development and to fuel antibiotic discovery efforts. This review will present recent case studies describing the total synthesis and biosynthesis of uridine natural products, and de novo synthetic efforts exploiting features of the natural products to produce simplified scaffolds. This research has culminated in the development of complementary strategies that can lead to effective uridine-based inhibitors and antibiotics. The strengths and challenges of the juxtaposing methods will be illustrated by examining select uridine natural products. Moreover, structure–activity relationships (SAR) for each natural product-inspired scaffold will be discussed, highlighting the impact on inhibitor development, with the aim of future uridine-based small molecule expansion.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.BMC.2020.115661
