MFROSPEP

Designing metallopeptides for the removal of superoxide radicals

 Coordinatore INSTITUTO DE TECNOLOGIA QUIMICA E BIOLOGICA - UNIVERSIDADE NOVA DE LISBOA 

 Organization address address: "Avenida da Republica, Estacao Agronomica Nacional"
city: OEIRAS
postcode: 2784-505

contact info
Titolo: Dr.
Nome: Olga
Cognome: Iranzo Casanova
Email: send email
Telefono: +351 21 4469736
Fax: +351 21 4411277

 Nazionalità Coordinatore Portugal [PT]
 Totale costo 100˙000 €
 EC contributo 100˙000 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-IRG-2008
 Funding Scheme MC-IRG
 Anno di inizio 2009
 Periodo (anno-mese-giorno) 2009-04-01   -   2013-03-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    INSTITUTO DE TECNOLOGIA QUIMICA E BIOLOGICA - UNIVERSIDADE NOVA DE LISBOA

 Organization address address: "Avenida da Republica, Estacao Agronomica Nacional"
city: OEIRAS
postcode: 2784-505

contact info
Titolo: Dr.
Nome: Olga
Cognome: Iranzo Casanova
Email: send email
Telefono: +351 21 4469736
Fax: +351 21 4411277

PT (OEIRAS) coordinator 100˙000.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

scaffolds    shows    hydrogen    diseases    native    sod    becoming    metalloenzymes    sods    antioxidant    disorders    population    reactive    denominator    stress    mechanisms    cells    health    defence    species    mn    metal    artificial    peroxide    death    toxic    neurodegenerative    dismutation    oxygen    evidence    imbalance    removal    therapeutic    dioxygen    mfrospep    structural    dismutases    basis    cardiovascular    oxidative    endogenous    mimics    generation    radicals    peptide    detrimental    binding    enzymes    implicated    designing    superoxide    global    burden    fe    considering    redox   

 Obiettivo del progetto (Objective)

'Oxidative stress results from an imbalance between the generation of reactive oxygen species and the antioxidant defense mechanisms. In recent years, oxidative stress has been implicated in a variety of detrimental health conditions including cardiovascular diseases, neurodegenerative disorders, and other types of age-related diseases. Evidence shows that the formation of superoxide radicals is a common denominator associated with all these conditions. Considering that cardiovascular diseases are the number one cause of death globally and neurodegenerative diseases are becoming a major health burden due to the aging of the global population, it is not surprising that a great deal of interest has been shown to develop new therapeutic approaches for scavenging these dangerous radicals. Superoxide dismutases (SODs) are endogenous metalloenzymes that catalyze the dismutation of these radicals into the less toxic dioxygen and hydrogen peroxide. Thus, they play a key role in cellular protection against oxidative stress conditions. The present proposal will focus on the design, synthesis and characterization of Mn/Fe SOD peptide mimics. The working hypothesis is that by designing peptides that contain the same metal binding sites as those present in the native SODs there is potential for developing novel structural and functional SOD mimics. To this aim, different native-like protein/peptide scaffolds will be prepared. Mn and Fe binding affinities, redox potentials and SOD activity will be determined for the different constructs with the objective of obtaining crucial structure-activity-redox relationships. The completion of this research will increase our understanding of the structural basis needed for the dismutation of superoxide radicals. As this understanding evolves and is further refined, it should allow us and other research groups to make inroads in designing more effective SOD mimics.'

Introduzione (Teaser)

Superoxide radicals are a common denominator in many disorders. To increase the antioxidant defence mechanisms, European researchers generated artificial enzymes that mimicked endogenous processes.

Descrizione progetto (Article)

Cardiovascular diseases are still the number one cause of death and neurodegenerative disorders are becoming a major global health burden particularly with the ageing of the population. Oxidative stress, originating from an imbalance between the generation of reactive oxygen species and the antioxidant defence mechanisms of cells, has been implicated in these diseases and evidence shows that a common denominator are superoxide radicals.

Given the prevalence of these diseases among the European population, the EU-funded 'Designing metallopeptides for the removal of superoxide radicals' (MFROSPEP) project aimed to find new therapeutic solutions. Researchers therefore decided to mimic the natural processes that take place within cells to fight against the detrimental effects of oxidative stress conditions.

Cells possess superoxide dismutases (SODs), endogenous metalloenzymes that convert superoxide radicals into the less toxic dioxygen and hydrogen peroxide. The MFROSPEP project aimed to replicate this process, known as dismutation, by developing novel and better antioxidant compounds. In this context, they formulated promising peptide scaffolds capable of binding redox active metal ions under physiological conditions. Their degrees of flexibility allowed the metal ion redox cycling needed for the catalytic removal of superoxide radicals and therefore, these metallopeptide systems showed potential to evolve as SOD mimics.

Overall, the MFROSPEP research increased our understanding of the key factors needed to develop antioxidant agents. The generated peptide systems will form the basis for the development of artificial SOD enzymes for therapeutic applications against cardiovascular and neurodegenerative disorders. Considering the economic health burden associated with neurodegeneration, implementation of the MFROSPEP deliverables could ameliorate part of the disease phenotype.

Altri progetti dello stesso programma (FP7-PEOPLE)

FMIA (2010)

Future Mobile Information Access: Challenges and Opportunities

Read More  

STEMMAD (2013)

Patient-specific stem cell-derived models for Alzheimer’s disease and related neurodegenerative disorders

Read More  

N2SOC (2010)

Natura 2000: a sociological study

Read More