Chemoenzymatic Synthesis of a Novel Sugar Scaffold for Targeting Ligand Development

Abstract

The capsular polysaccharides (CPSs) that encapsulate bacteria aids in overall virulence of the microbe. The bacterial capsules differ across species of bacteria from benign, pathogenic, or symbiotic bacteria. Specific targeting of the surface of the differing organisms would be advantageous in order to select certain types of bacteria over others, for either targeting or detection purposes.In our lab, we have developed a new strategy to specifically target surfaces of certain types of bacteria. The developed targeting strategy is based on the surface coating of Vibrio vulnificus, and specifically the rare N‐acetyl‐quinovosamine (QuiNAc) sugar contained in the sugar polymer, as well as other sugars from the V. vulnificus polysaccharide biosynthesis pathway. The targeting strategy involves naturally occurring enzyme sugar products, as well as an isoprenoid anchor analogue that was developed for use with elucidation of polysaccharide biosynthesis pathways in our lab.Determination of the sugar linkage to the isoprenoid anchor has been analyzed by RP‐HPLC with the use of a modified fluorescent isoprenoid analogue. A further developed analogue has been synthesized in our lab, which contains a different reactive group. This reactive group is used in the development of the targeting ligand for the rare QuiNAc sugar. Following the development of the targeting ligand associated with the rare sugars on specific types of bacteria, the use of the targeting agent is useful in applications of bacterial detection or in antibacterial schemes.Support or Funding InformationNational Institutes of Health AREA Grants R15GM100402 (J.M.T.), R15GM114773 (J.M.T.) and National Science Foundation Instrumentation Grant 1337873 (UNC‐Charlotte Chemistry)