CYSTEINE-FREE NCL
Development of a new methodology for the synthesis of mercapto amino acids for protein synthesis by cysteine-free native chemical ligation
| Coordinatore | FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Organization address
address: CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA contact info |
| Nazionalità Coordinatore | Spain [ES] |
| Totale costo | 173˙370 € |
| EC contributo | 173˙370 € |
| 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-2013-IIF |
| Funding Scheme | MC-IIF |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-04-14 - 2016-04-13 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Organization address
address: CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA contact info |
ES (BARCELONA) | coordinator | 173˙370.60 |
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Obiettivo del progetto (Objective)
'Proteins are in the heart of almost every single biological function and therefore are essential tools for drug discovery. Although the use of recombinant DNA techniques has been successfully applied to the synthesis of many proteins, the access to proteins bearing non natural amino acids, naturally obtained through post-translational modifications, remains limited. However, with the invention of Solid Phase Peptide Synthesis (SPPS) by Merrifield, the total chemical synthesis of peptide containing non-proteinogenic amino acids can be easily achieved. Nonetheless, the SPPS technique is only suitable for peptide chains of a length below 50 amino acids. The problem related to the synthesis of large peptide or even proteins was overcome by Kent et al. who were able to link peptide fragments together by Native Chemical Ligation (NCL). NCL involves the reaction between the N terminus cysteine of a first fragment and the thioester C-terminus of a second fragment. After the transthioesterification, a S -> N acyl transfer yields the desired native amide bond. Despite this ground-breaking discovery, NCL remains limited to cysteine-containing proteins. In 2001, Dawson et al. introduced the ligation-desulfurisation technique. This latest advance paved the way to cysteine free NCL and prompted many research groups to focus their efforts on the preparation of beta- and gamma-mercapto amino acids for use in ligation-desulfurisation strategy. Unfortunately, the 7 to 16 steps required for their synthesis considerably restrain their uses by peptide chemists. The proposed project is directed towards the elaboration of a straightforward synthetic route to access beta-thiol amino acids from a single precursor using the latest breakthroughs in C-H activation technique. In order to demonstrate the usefulness of these novel building blocks for the synthesis of proteins, these cysteine surrogates will be employed in the synthesis of the cysteine-free anti-HIV protein, Griffithsin.'