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

Protease susceptibility II

a tropoelastin and susceptibility technology, applied in the field of tropoelastin susceptibility ii, can solve the problems of inadequate or faulty elastin fiber repair at the site of injury, the soluble precursor of elastin is far more susceptible to proteolysis, and the elastin molecule is not shown in the study

Inactive Publication Date: 2008-03-06
APTALIS PHARMA
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to modifying the amino acid sequence of tropoelastin, a precursor of elastin, to make it more resistant to proteolysis. The invention includes manipulating the protease susceptibility of tropoelastin by creating peptidomimetic molecules that contain the same amino acid sequences as the protease-susceptible parts of tropoelastin. The invention also includes creating peptidomimetic molecules that contain modified protease susceptibility sequences. The invention further includes using serine protease inhibitors to prevent degradation of tropoelastin. The invention also includes identifying the specific proteases that are responsible for degrading tropoelastin and using them to develop better inhibitors of proteolysis. The invention also includes identifying the regions of cleavage for plasmin and trypsin. The invention also includes analyzing the effect of protease inhibitors on serum degradation of tropoelastin. Overall, the invention provides methods for protecting and manipulating tropoelastin to improve its resistance to proteolysis and elastin peptides.

Problems solved by technology

However, tropoelastin, the soluble precursor of elastin, is far more vulnerable to proteolysis.
However, proteolysis could also result in inadequate or faulty elastin fiber repair at the site of injury.
However, none of these studies has provided indication of where the tropoelastin molecule is cut by proteases.

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
  • Protease susceptibility II
  • Protease susceptibility II
  • Protease susceptibility II

Examples

Experimental program
Comparison scheme
Effect test

examples

Materials and Methods

Reagents

[0140] Hirudin, PMSF, human thrombin, human plasma kallikrein, human plasmin and human leukocyte elastase (HLE) were obtained from Sigma. Bovine trypsin and Pefabloc SC were from Boehringer-Mannheim and Pefabloc PK was from Pentapharm, Switzerland. Gelatinase A (72 kDa gelatinase) and gelatinase B (92 kDa gelatinase) were obtained from Boehringer Mannheim Roche Diagnostics.

[0141] SHEL was obtained by the method described in WO94 / 14958.

[0142] SHELδ26A can be derived from SHEL by removing the synthetic coding sequence corresponding to exon 26A. A comparison of the sequence of SHEL with that of SHELδ26A is provided at FIG. 3. Its protein product is apparently identical to a naturally made human splice form of tropoelastin.

[0143] The Transformer Mutagenesis Kit (Clontech USA) was used with pSHELF (described in WO94 / 14958) in accordance with the supplied protocol to remove DNA corresponding to exon 26A. The sequence of the mutagenic primer used (manufac...

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
total volumeaaaaaaaaaa
pHaaaaaaaaaa
Login to View More

Abstract

The manipulation of the amino acid sequence of tropoelastin, particularly human tropoelastin, to modify its protease susceptibility is described. The modified tropoelastins include tropoelastin derivatives having modified protease susceptibility, peptidomimetic molecules which contain amino acid sequences which correspond to or incorporate the protease susceptible sequences of tropoelastin. Uses of these tropoelastin derivatives and peptidomimetic molecules are provided. Also provided are nucleic acid molecules and genetic constructs encoding the amino acid sequences of the derivatives and peptidomimetic molecules of the invention.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 09 / 743,818, filed Apr. 26, 2001, which is a 371 of PCT / AU99 / 00580, filed Jul. 19, 1999.BACKGROUND OF THE INVENTION [0002] The present invention relates to: manipulation of the amino acid sequence of tropoelastin, particularly human tropoelastin, to modify its protease susceptibility; to tropoelastin derivatives having modified protease susceptibility; to peptidomimetic molecules which contain amino acid sequences which correspond to or incorporate the protease susceptible sequences of tropoelastin; and to uses of the tropoelastin derivatives and peptidomimetic molecules. [0003] The invention also relates to nucleic acid molecules and genetic constructs encoding the amino acid sequences of the derivatives and peptidomimetic molecules of the invention. [0004] The insoluble cross-linked elastin molecule is highly resistant to proteolytic degradation by many proteases. H...

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): A61K38/00A61P43/00C07K14/00C07K7/00C12N15/09A61K38/17A61L27/00C07H21/04C07K7/02C07K7/04C07K14/78C07K19/00C12N1/15C12N1/19C12N1/21C12N5/10C12N15/12C12P21/02
CPCA61K38/00C07K14/78C07K7/02A61P43/00
Inventor WEISS, ANTHONY STEVEN
Owner APTALIS PHARMA
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