Dr James Redman Project Titles
1. Synthesis, Analysis and Biological Activity of Cyclic Peptides
Cyclic peptides have a more constrained geometry and greater protease resistance than linear peptides with the same amino acid sequence. These properties can confer advantages for biological activity, and indeed a number of cyclic peptides are employed as drugs. This project will include synthetic organic chemistry and cyclic peptide analysis by mass spectrometry. There will be the opportunity to develop methods for mass spectrometric sequencing of cyclic peptides and to assess the biological activity of the peptides, for example their ability to stimulate an immune response.
2. Small Molecules for Perturbing RNA Interactions in Cells
Messenger RNA (mRNA) molecules are capable of folding intramolecularly to generate secondary structure that may regulate gene expression. In addition, some mRNAs may form a duplex with a complementary ‘antisense’ strand that is transcribed from the opposite strand of the DNA template. The role of natural antisense RNAs in controlling translation and stability of the mRNA is presently under scrutiny. This project involves design, synthesis and testing of molecules which will disturb secondary structures in mRNA in an effort to probe these structures’ roles in gene regulation.
3. Synthesis of Amino Acids as Building Blocks for Nucleic Acid Binding Peptides
Various drugs operate by binding to nucleic acid targets. For example, the aminoglycoside class of antibiotics bind to ribosomal RNA thus interfering with bacterial protein synthesis, and certain anticancer drugs function by binding DNA through aromatic stacking, electrostatic and hydrogen bonding interactions. Amino acid building blocks with aromatic and positively charged side chains can be readily assembled into peptides which have a propensity for binding to nucleic acids. This project will investigate the synthesis of amino acids with side chains designed to make attractive interactions with DNA and RNA. The project will involve primarily synthetic organic chemistry and there will be the opportunity to perform binding assays to investigate the interactions of the new compounds with nucleic acids.