Probing JNK MAPK function with peptide inhibitors. It has generally been accepted that the JNK MAPK family of protein kinases is rapidly and potently activated following the exposure of mammalian cells to stresses and cytokines. However, their biological role has remained controversial. We believe that this problem reflects the lack of a generally applicable and specific JNK MAPK inhibitor. In this project we continue our characterisation of a small peptide inhibitor developed in our laboratori ....Probing JNK MAPK function with peptide inhibitors. It has generally been accepted that the JNK MAPK family of protein kinases is rapidly and potently activated following the exposure of mammalian cells to stresses and cytokines. However, their biological role has remained controversial. We believe that this problem reflects the lack of a generally applicable and specific JNK MAPK inhibitor. In this project we continue our characterisation of a small peptide inhibitor developed in our laboratories. We aim to determine its mechanism of inhibition, the specificity of interaction, and to evolve more effective inhibitors. With these new inhibitors, we can effectively address the biological roles of these kinases.Read moreRead less
In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-sele ....In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-selective incorporation are inefficient. The project’s strategy relies on the depletion of selected tRNAs from an in vitro protein translation system and their replacement with synthetic tRNAs, charged with unnatural amino acids. It is expected that the developed technology could be used to rapidly generate and screen highly diversified macrocyclic peptide libraries.Read moreRead less