Trehalose is a naturally occurring disaccharide that is a versatile bioprotectant, as it is used as an additive in many industries including food, cosmetics, and pharmaceuticals, and has been studied as a possible therapeutic for neurodegenerative and cardiometabolic diseases. However, trehalose  is susceptible to degradation by enzymes known as trehalases, which are present in many organisms, including humans and microbes. Degradation can diminish treahlose’s ability as a therapeutic and potentially contribute to the virulence of pathogenic bacteria in the gut. The goal of this project is to develop degradation-resistant trehalose analogues that can withstand breakdown by trehalases. A panel of trehalose analogues with systematic chemical modifications was synthesized using chemical and chemoenzymatic approaches. Next, the analogues were tested against mammalian and microbial trehalases using a thin layer chromatography assay. It was found that most of the analogues were largely resistant to the trehalases tested, suggesting that these enzymes have a high level of specificity for the native substrate. A few of the analogues, including 2-epimeric-, 2-deoxyfluoro-, and 6 azidodeoxy-trehalose, were not detectably degraded by any trehalases, indicating broad resistance to trehalase-catalyzed hydrolysis. On the other hand, some analogues, including 5-thio-trehalose, showed variable resistance across the enzyme panel. Together, these results elucidated substrate tolerance of several trehalases and identified trehalose analogues that may be useful for medical or biotechnology applications in which enzymatic degradation is a concern.

Synthesis and evaluation of degradation-resistant trehalose analogues for biomedical and biotechnological applications

ACS Spring 2022

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