NCB-TNT

New chemical biology for tailoring novel therapeutics

 Coordinatore THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 2˙499˙991 €
 EC contributo 2˙499˙991 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-ADG
 Funding Scheme ERC-AG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-03-01   -   2019-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    THE UNIVERSITY COURT OF THE UNIVERSITY OF ABERDEEN

 Organization address address: KING'S COLLEGE REGENT WALK
city: ABERDEEN
postcode: AB24 3FX

contact info
Titolo: Ms.
Nome: Crystal
Cognome: Anderson
Email: send email
Telefono: +44 1224 274103
Fax: +44 1224 272319

UK (ABERDEEN) beneficiary 525˙761.00
2    THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS

 Organization address address: NORTH STREET 66 COLLEGE GATE
city: ST ANDREWS FIFE
postcode: KY16 9AJ

contact info
Titolo: Ms.
Nome: Trish
Cognome: Starrs
Email: send email
Telefono: +44 1334 467286
Fax: +44 1334 442217

UK (ST ANDREWS FIFE) hostInstitution 1˙974˙230.00
3    THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS

 Organization address address: NORTH STREET 66 COLLEGE GATE
city: ST ANDREWS FIFE
postcode: KY16 9AJ

contact info
Titolo: Prof.
Nome: James Henderson
Cognome: Naismith
Email: send email
Telefono: +44 1334 463792
Fax: +44 1334 462217

UK (ST ANDREWS FIFE) hostInstitution 1˙974˙230.00

Mappa


 Word cloud

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

peptide    macrocycles    enzymes    scaffolds    power    amino    acids    solid    cyanobactin    containing    medicines    structural    residue    modified    macrocyclases    substrates    protein    twenty    ability    peptides    family    cyclic    natural    diverse    six   

 Obiettivo del progetto (Objective)

'Most of our drugs derive from natural products, many more natural products possess biological activity but our inability to synthesise novel analogues hampers our ability to use them either as tools or medicines. Cyclic peptides are common structural motifs in natural products and medicines (vancomycin, gramicidin). They are widely recognised to constitute a promising and still underexploited class of molecule for novel therapeutics; specifically an important role for cyclic peptides in the inhibition of protein-protein interactions has been demonstrated. We will harness the power of the recently identified macrocyclases from the ribosomally-derived cyanobactin superfamily to prepare diverse modified cyclic peptides. These enzymes exhibit the remarkable ability to macrocyclise unactivated peptide substrates. Different members of this family of macrocyclases process peptides into macrocycles containing from six up to twenty residues. We have characterised and re-engineered one member of the family (PatG) which makes eight residue macrocycles. We will determine the structural and biochemical features of the macrocyclases that are known to lead to six or to twenty residue macrocycles. We will use these insights to put these enzymes to work in novel chemical reactions. We will combine macrocyclases with other enzymes from the cyanobactin biosynthetic pathways (whose structures and mechanism we have largely determined) and work on solid phase peptide substrates. By bringing together the power of solid phase methods (split and pool) and the novel chemistry enabled by the enzymes, we will generate highly diverse macrocyclic scaffolds containing amino acids, enzymatically modified amino acids, non-natural amino acids and non-amino acid building blocks. Successful completion of the project will revolutionise the design of cyclic peptide-inspired libraries with diverse backbone scaffolds for applications in target identification, drug discovery and tool screening.'

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