CNRS Technologies

Find the best CNRS technologies to boost your innovative project.

Newest patents

You are a research scientist?

We can guide you through the whole technology transfer process.

See all our services

You are a corporate player?

Thanks to our expertise, our network and our know-how of the innovation ecosystem, we support you throughout your project.

Contact us

Follow our news and upcoming events

Discover CNRS technologies

Meet our team

Close

A new class of compounds, inhibitors of advanced glycation end-products (AGE) formation, to prevent the deleterious effects of aging due to the formation of AGE

Reference

01418-01

Patents status

French priority patent application n° FR0503176 filed on March 31th, 2005 and entitled ” Inhibiteurs d’AGE ”

Inventors

Joanna BAKALA
Pierre POTIER
André SASAKI-NOBUMICHI
Maria Conception ACHAB
Qian WANG ZHU
Loudmila ERMOLENKO
Gisèle FRANCK
Naima NHIRI

commercial status

Exclusive or non-exclusive licenses, Collaborative agreement

Laboratory

Institut de Chimie des Substances Naturelles, (ICSN,UPR2301) in Gif sur Yvette, France. 

Description

CONTEXT

AGE are a heterogeneous group of molecules formed within the body during aging and, at an accelerated rate, in diabetes. AGE result from the non-enzymatic reaction of proteins, lipids, and nucleic acids with reducing sugars such as glucose but mainly with compounds containing reactive carbonyl groups [the most reactive a-dicarbonyls are glyoxal (GO) and methylglyoxal (MG)]. The AGE deteriorate the structure and impairs the biological function of the implicated biomolecules leading consequently to the cellular damages. In vivo and in vitro studies show that AGE affect also cellular signalling and gene expression. The generation of AGE contributes mainly to diabetes related complications and chronological aging. In view of deleterious consequences of AGE formation, numerous agents preventing AGE accumulation were investigated. Therapeutic interventions for reducing AGE might target their formation by decreasing the level of a-dicarbonyls.

TECHNICAL DESCRIPTION

This invention describes the synthesis and the biolgical activites of new class of N-terminal diaminopropionic acid (Dap) peptides. These molecules were identified as the highly reactive scavengers of a-dicarbonyl compounds. They inhibit in vitro glycation process induced by methylglyoxal (MG) of a number of proteins (insuline, glyoxalase I, actine, tubuline, lysozyme, SOD, RNase, somatostatine). The in vitro expositions of all studied proteins to MG in the presence of N-terminal Dap peptides allow preserving their structure and biological activity. Moreover, these peptides protect endothelial cells and human keratinocytes against cytotoxicity induced by MG. The results of ex vivo studies realized on the explants of human skin treated with MG show that N-terminal Dap peptides totally inhibit the formation of AGE (Ne-carboxymethyl-lysin (CML) and pentosidin) induced by MG. Furthermore, topical treatment of ex vivo cultured skin explants with one of N-terminal Dap peptides increases the thickness of the epidermis and upregulates the synthesis of collagen I and III as well as the glycoaminoglycans (GAGs). Mutagenic activities of tested peptides and their metabolites according to the Ames assay are negative.

INDUSTRIAL APPLICATIONS

Cosmetic use of N-terminal Dap peptides as anti-aging agents.
Pharmaceutical use of N-terminal Dap peptides to treat the diseases as well as the deleterious effects due to the formation of AGE.

DEVELOPMENT STAGE

The experimental approches  used :
Structural modifications : RP-HPLC analysis, SDS/PAGE electrophoresis
Biological activities : ELISA, studies of enzymatic activity, studies of peptides stability (pH 3.5-6.5), cell culture of endothelial cells (EA.hy926) and human keratinocytes, ex vivo human skin explants assay, histology and immune-histochemistry.
For further information, please contact us (Ref 01418-01)

Need further information ?

Contact us
Close

Contact us

  • This field is for validation purposes and should be left unchanged.
Close

Newest patents