CYCLOTIDE MECHANISM

Elucidating the mechanism of action of cyclotides: ultra-stable proteins from plants

Coordinatore	INSTITUTO DE MEDICINA MOLECULAR    more  Organization address address: AVENIDA PROF EGAS MONIZ city: LISBOA postcode: 1649 028 contact info Titolo: Dr. Nome: Margarida Cognome: Pinto Gago Email: send email Telefono: 351218000000 Fax: 351218000000
Nazionalità Coordinatore	Portugal [PT]
Totale costo	222˙590 €
EC contributo	222˙590 €
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-2007-4-1-IOF
Funding Scheme	MC-IOF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-01-01   -   2011-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUTO DE MEDICINA MOLECULAR  Organization address address: AVENIDA PROF EGAS MONIZ city: LISBOA postcode: 1649 028 contact info Titolo: Dr. Nome: Margarida Cognome: Pinto Gago Email: send email Telefono: 351218000000 Fax: 351218000000	PT (LISBOA)	coordinator	0.00

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 Obiettivo del progetto (Objective)

'The utility of conventional peptides in pharmaceutical and biotechnological applications is limited by their poor stability and bioavailability. Cyclotides are plant derived mini-proteins with unique structural properties that make them exceptionally stable and have a range of exciting applications in drug design and agriculture. Beside the variety of intrinsic activities, there are still many unanswered questions regarding the mechanism involved in cyclotides activity. Understanding how they exert their biological effects is a crucial step and is the basis of this proposal. Recent evidence has emerged that these actions are mediated by membrane interactions and this study will determine the chemical and biophysical basis for these interactions. The main goal of this project is to explore the interaction of a selected set of cyclotides with biological membranes. The specific objectives are to evaluate: 1) the structural features important for the membrane binding of cyclotides; 2) the structural basis of membrane selectivity; 3) if the self-association properties of cyclotides are involved in their mechanism of action; 4) the biophysical basis for the effects of cyclotides on living cells; 5) the information from objective 1-4, together with bioactivity data to rationalise the bioactivity of cyclotides. Understanding how cyclotides exert their biological activities will provide valuable information that can be applied in subsequent drug design studies. The outgoing host lab has a strong background on cylotides and several facilities that can be optimized for peptide-lipid studies (NMR and fluorescence spectroscopies, isothermal titration calorimetry and surface Plasmon resonance). An advanced training to complement applicant specific expertise and skills in peptide-lipid interaction, obtained previously in return host lab, will be acquired. This knowledge exchange between outgoing and return host organization will create an environment for future collaborations.'