Streptococcus mutans is a pathogenic bacterium that gives rise to the formation of dental caries, the most prevalent childhood disease. Specifically, S. mutans forms biofilm on the various surfaces in the oral cavity which leads to acidification and subsequent erosion of the dental enamel. Previously, we have studied the natural product carolacton (1) in the context of its anti-biofilm activity and developed a library of carolacton-inspired analogs. Herein we disclose the synthesis and biological investigation of our novel, more potent, biofilm inhibitor (2), as well as its use as a chemical tool to further understand the biofilm mechanisms involved in the action of these macrocyclic compounds. Target identification via affinity-based protein profiling (ABPP) and resistance selection assays were used to identify the protein target for (2). Furthermore, these results have implications in understanding complex biofilm mechanisms of the pathogenic bacteria, S. mutans, and other biofilm-mediated diseases. Combined these results demonstrate the power of chemical synthesis in elucidating the underpinnings of microbial pathogenesis.

Synthetic simplification of carolacton leads to identification of novel biofilm target

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.