Feedback Prodrugs
- *Abstract
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Application
Prodrugs are often used to minimize toxicity problems foundwith therapeutic compositions for a myriad of conditions. It has historically difficult to develop bothdrugs and prodrugs for inhibitors of glycosidases, which are involved in manyvital cellular functions. Describedherein is a feedback prodrug approach for glycosidase inhibitors which addressmany of the above issues.
- Glycosidase inhibitor is released by thetargeted glycosidase
- Relevant for therapeutic medical and veterinaryapplications (cancer; diabetes, hepatitis, viral infections, bacterialinfections, fungal infections, genetic disorders, and lysosomal storagediseases)
- Could be used for clinical diagnosis orassay kit
- Agrochemical applications such as controlof insects or fungus
ProblemsAddressed
- Chemical modification of a lead compound incombination with a feedback prodrug formulation may make it easier to developglycosidase inhibitors as safe therapeutics
- Prodrug displays high specificity of action, areduced toxicity, an improved stability in serum and blood, and moves intotarget cells minimally unless activated by a target cell associated enzyme
- Prodrug is expected to be effective forreducing the activity of the lytic enzyme in vitro and in vivo
- The prodrug can be administered to anysubject including humans and domesticated animals
- The approach is not limited to glycosidasetargets and it is to be expected to be applied to the design of inhibitors ofother classes of enzymes such as proteases and kinases
TechnologySummary
University of Georgia researchers have developed a prodrugin the form of a conjugated compound that serves as a substrate for a lyticenzyme and includes, as a direct or indirect cleavage product, an inhibitor ofthat enzyme. Contact between the prodrugand the lytic enzyme releases the inhibitor and thereby inhibits the activityof the lytic enzyme through feedback inhibition.
The attraction of this approach is that the inhibitor willonly be released at the site of the enzyme. Selectivity is achieved due to the specific selectivity of glycosidasesfor their substrates. Furthermore, onlythe amount of compound required for complete inhibition of the targeted enzymeis released. The remaining pool ofprodrug will, however, be activated when active enzyme reappears therebyapproximating conditions of continual infusion.
Inventors
• Geert-JanBoons, Distinguished Professor in Biochemical Sciences
• JunGuo
• JinkengAsong
The research of the Boons Group deals with thesynthesis and biological functions of carbohydrates and glycocongugates. Thediversity of topics to which the group has significantly contributed includethe development of new and better methods for synthesizing exceptionallycomplex molecules, the use of new methods in the synthesis and study ofproperties of complex carbohydrates of increasing size and complexity, thedevelopment of synthetic cancer and bacterial vaccines, the design andsynthesis of glycosidase inhibitors and the use of synthetic compounds for thestudy of innate immunity
- *IP Issue Date
- None
- *IP Type
- Utility
- 国家
- United States
- 申请号码
- 8,796,229
- 国家/地区
- 美国
