Presenter: Mia Ramos – Biochemistry
Faculty Mentor(s): Annie Gilbert, Mike Pluth
Session: (In-Person) Poster Presentation
Hydrogen sulfide (H2S) is a small gaseous signaling molecule that can provide a variety of important physiological effects. For example, H2S can promote angiogenesis, osteogenesis, and regulate inflammation. These regenerative effects of H2S make it an ideal therapeutic candidate for healing bone defects. The challenge with studying therapeutic effects of H2S in bone applications is that the direct delivery of H2S as a gas or inorganic sulfide salt lack spatial and temporal control. To address this challenge, small molecule H2S donors have been developed. Previously, the Pluth lab has developed caged thiocarbamates as a highly tunable class of COS-based H2S donors. Upon activation, caged thiocarbamates undergo a self-immolative cascade in the presence of specific environments or analytes to produce COS, which is rapidly converted to H2S by carbonic anhydrase. This strategy could be useful for localizing H2S delivery in bone healing sites. Alkaline phosphatase (ALP) is an enzyme that is present in large concentrations in bone fractures and could serve as an activator of H2S production from a phosphate protected caged thiocarbamate. Here, we developed an alkaline phosphatase-activated caged thiocarbamate COS/H2S donor to study H2S in bone healing applications. We anticipate the development of these ALP-activated H2S donors will serve as useful tools for investigating therapeutic effects of H2S in bone healing.