Innovation Sphere

Projects Sharing Researchers

Researchers

  • Gerardus Boons
  • Jun Guo
  • Jinkeng Asong

Communicate

Details

Project TitleFeedback Prodrugs
Track Code1231
Short Description
Abstract

Application

Prodrugs are often used to minimize toxicity problems found with therapeutic compositions for a myriad of conditions.  It has historically difficult to develop both drugs and prodrugs for inhibitors of glycosidases, which are involved in many vital cellular functions.  Described herein is a feedback prodrug approach for glycosidase inhibitors which address many of the above issues.

  •  Glycosidase inhibitor is released by the targeted glycosidase
  • Relevant for therapeutic medical and veterinary applications (cancer; diabetes, hepatitis, viral infections, bacterial infections, fungal infections, genetic disorders, and lysosomal storage diseases)
  • Could be used for clinical diagnosis or assay kit
  • Agrochemical applications such as control of insects or fungus

Problems Addressed

  • Chemical modification of a lead compound in combination with a feedback prodrug formulation may make it easier to develop glycosidase inhibitors as safe therapeutics
  • Prodrug displays high specificity of action, a reduced toxicity, an improved stability in serum and blood, and moves into target cells minimally unless activated by a target cell associated enzyme
  • Prodrug is expected to be effective for reducing the activity of the lytic enzyme in vitro and in vivo
  • The prodrug can be administered to any subject including humans and domesticated animals
  • The approach is not limited to glycosidase targets and it is to be expected to be applied to the design of inhibitors of other classes of enzymes such as proteases and kinases

Technology Summary

University of Georgia researchers have developed a prodrug in the form of a conjugated compound that serves as a substrate for a lytic enzyme and includes, as a direct or indirect cleavage product, an inhibitor of that enzyme.  Contact between the prodrug and the lytic enzyme releases the inhibitor and thereby inhibits the activity of the lytic enzyme through feedback inhibition. 

The attraction of this approach is that the inhibitor will only be released at the site of the enzyme.  Selectivity is achieved due to the specific selectivity of glycosidases for their substrates.  Furthermore, only the amount of compound required for complete inhibition of the targeted enzyme is released.  The remaining pool of prodrug will, however, be activated when active enzyme reappears thereby approximating conditions of continual infusion.

Inventors

•         Geert-Jan Boons, Distinguished Professor in Biochemical Sciences

•         Jun Guo

•         Jinkeng Asong

 

The research of the Boons Group deals with the synthesis and biological functions of carbohydrates and glycocongugates. The diversity of topics to which the group has significantly contributed include the development of new and better methods for synthesizing exceptionally complex molecules, the use of new methods in the synthesis and study of properties of complex carbohydrates of increasing size and complexity, the development of synthetic cancer and bacterial vaccines, the design and synthesis of glycosidase inhibitors and the use of synthetic compounds for the study of innate immunity

https://www.ccrc.uga.edu/~gjboons/boons/Home.htm

 
TagsCarbohydrate, Drug Manufacturing
 
Posted DateJul 5, 2017 10:38 AM

Researcher

Name
Gerardus Boons
Jun Guo
Jinkeng Asong

Manager

Name
Rachael Widener

Intellectual Property

Patent Number Issue Date Type Country of Filing
8,796,229 None Utility United States