Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Feedback Prodrug

a prodrug and feed technology, applied in the field of feedback prodrug, can solve the problems of rarely achieving selective inhibitors, small number of glycosidase inhibitors have been successfully developed as therapeutics, and inhibit a wide range of glycosidase inhibitors, etc., to facilitate cellular uptake and improve selectivity

Inactive Publication Date: 2010-06-24
UNIV OF GEORGIA RES FOUND INC
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The invention provides compounds and methods for selectively inhibiting a lytic enzyme based on feedback inhibition. These compounds are prodrugs that are released by the enzyme they inhibit, resulting in improved selectivity. The prodrug can be O-acetylated to facilitate cellular uptake. The compounds can be used in therapeutic medical and veterinary applications, as well as in agricultural applications such as control of insects or fungus. The first constituent of the conjugated compound can include a carbohydrate or polypeptide moiety, and the second constituent can include an inhibitor moiety that inhibits the activity of a glycosidase, protease, or kinase. The compounds can be administered to humans or animals to treat various diseases or conditions, or to plants as insecticides or fungicides."

Problems solved by technology

A serious drawback of the use of these alkaloids as drugs is that they inhibit a wide range of glycosidases.
Although many analogs of natural glycosidase inhibitors have been synthesized, these efforts have rarely resulted in a selective inhibitor.
As a result, only a very small number of glycosidase inhibitors have been successfully developed as therapeutics.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Feedback Prodrug
  • Feedback Prodrug
  • Feedback Prodrug

Examples

Experimental program
Comparison scheme
Effect test

examples

[0053]The present invention is illustrated by the following examples. It is to be understood that the particular examples, materials, amounts, and procedures are to be interpreted broadly in accordance with the scope and spirit of the invention as set forth herein.

example i

Selective Inhibition of Glycosidases by Feedback Prodrugs

[0054]We report here a general approach for the design and synthesis of selective glycosidase inhibitors based on feedback inhibition. Feedback inhibition is a mechanism in which a biosynthetic pathway regulates itself through inhibition of the first committed step in the pathway by a down stream or final product (Pardee et al., Gene 2003, 321, 17). Although this type of inhibition is widely used in nature, it has not been exploited for the design and synthesis of selective therapeutics. The feedback inhibition prodrugs described here are composed of an inhibitor that is modified by a linker that renders them inactive (Scheme 1a; FIG. 1). The linker, in turn, is attached to a glycoside that can be hydrolyzed by a targeted glycosidase. The resulting intermediate is designed in such a way that it will undergo self-fragmentation to release the active inhibitor. Subsequently, the inhibitor will inhibit the enzyme that initiated it...

example ii

Design and Synthesis of Selective Glycosidase Inhibitors

[0082]Cells that have undergone oncogenic transformation often display abnormal cell surface oligosaccharides. These changes in glycosylation are important determinants of the stage, direction and fate of tumor progression. Inhibition of the mannose trimming enzyme human Golgi α-mannosidase II (HGMII), which acts late in the N-glycan processing pathway, provides one route to blocking the oncogene-induced changes in cell surface oligosaccharide structures.

[0083]A serious side effect of most mannosidase inhibitors is, however, the blockage in oligosaccharide catabolism arising from inhibition of a related catabolic α-mannosidase found in lysosomes. The development of a drug appropriate for anti-metastatic therapy requires a compound which specifically inhibits Golgi α-mannosidase II without affecting the function of lysosomal mannosidase (HLM). Many of the known glycosidase inhibitors exhibit low selectivity. For example, FIG. 5 ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
pHaaaaaaaaaa
pHaaaaaaaaaa
temperatureaaaaaaaaaa
Login to View More

Abstract

Compounds and methods for use in selectively inhibiting a lytic enzyme based on feedback inhibition. The conjugated compound serves as a substrate for a lytic enzyme. Cleavage of the conjugated compound by the lytic enzyme releases an inhibitor of the enzyme.

Description

[0001]This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 774,009, filed Feb. 16, 2006, which is incorporated herein by reference in its entirety.STATEMENT OF GOVERNMENT RIGHTS[0002]This invention was made with government support under a grant from the National Cancer Institute, National Institutes of Health, Grant No. 5U01CA91295. The U.S. Government has certain rights in this invention.BACKGROUND[0003]Protein- and lipid-linked oligosaccharides at the surface of eukaryotic cells are responsible for a wide range of biological processes impacting health and disease. Examples of such processes include fertilization, embryogenesis, neuronal development, hormone activities, the proliferation of cells and their organization into specific tissues. Remarkable changes in cell-surface carbohydrates occur with tumor progression, which appears to be intimately associated with the dreaded state of metastasis. Furthermore, carbohydrates of host cells are often employe...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00C07H1/00C07K2/00A61K31/70
CPCA61K47/48138A61K47/556A61P1/16A61P31/04A61P31/10A61P31/12A61P35/00A61P3/10
Inventor BOONS, GEERT-JANGUO, JUN
Owner UNIV OF GEORGIA RES FOUND INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com