Honours Projects in the Supramolecular Chemistry and Synthesis

Honours Projects in the Supramolecular Chemistry and Synthesis Group kate. jolliffe@sydney. edu. au Synthetic and Supramolecular Chemistry My research group focuses on the design, synthesis and investigation of the properties of functional molecules. It spans a number of areas including (i) the synthesis and investigation of small molecule mimics of Nature’s molecular receptors and enzymes (supramolecular chemistry); (ii) the development of new synthetic methods and (iii) application of these methods to the synthesis of both natural products and novel functional molecules. All projects involve synthesis, with some also involving physical and/or biological techniques. The information below gives an indication of our general areas of research. A number of collaborative projects are also available. Anion Sensors and Transporters for Environmental and Biological Applications Anions play important roles in areas as diverse as biology, medicine, catalysis and the environment. For example, phosphate anions, such as ATP, c. AMP and pyrophosphate, are essential in biological processes, and imbalances in levels can be a cause or effect of disease. For example, pyrophosphate levels in synovial fluid are much higher in arthritic than in healthy patients, while thiamine pyrophosphate levels are a marker of Vitamin B 1 deficiency. Several projects are available in this area, including: (i) the synthesis and evaluation of new receptors for sulfate ions for use in detection of sulfate levels in wastewater; (ii) harnessing the potential of fluorescent anion receptors to develop simple protocols for studying phosphate anions in biological systems; (iii) designing new receptors for binding to biologically important dicarboxylates such as oxo-glutarate and 2 -hydroxyglutarate and (iv) exploiting the power of sensing arrays to detect multiple anions in a single experiment (with Liz New). (v) Designing new receptors to discriminate between nucleoside phosphates (e. g ATP and ADP) Highly selective fluorescent and colourimetric peptide based receptors for pyrophosphate (PPi) Sulfate bound by a macrocyclic receptor with better selectivity than the sulfate binding protein These projects will suit students with interests in the use of NMR, UV-vis and fluorescence to study supramolecular systems, and can include synthetic and/or biological studies. Sensors for phospholipids Living cells synthesise and metabolise over 1000 different lipids, which assemble to form bilayer membranes with lipid compositions that differ across cell types, sub-cellular compartments and even within a single membrane itself. However, the relevance of this vast structural diversity and the function of each different lipid is not yet understood. In order to provide information answering this important biological question, fluorescent probes that are selective towards different phospholipid headgroups are required. This project will involve the synthesis of novel sensors for phospholipid headgroups such as phosphatidylcholine and phosphatidylethanolamine. The selectivity of the sensors will be established in model membranes using fluorescence spectroscopy, then selective sensors will be evaluated in biological assays. Phosphatidylserine detection in the membrane of an apoptotic cell Sensors and affinity resins for posttranslationally modified proteins sulfation Post-translational modifications (PTMs) such as phosphorylation, sulfation or methylation are crucial for the regulation of protein function. The identification of these PTMs provides a key method for determining how small modifications alter protein function. However, some modifications are difficult to detect because they are only present in very low quantities or may be lost using current protein purification methods. This project will involve the design and synthesis of selective receptors for PTMs such as sulfation. The receptors will then be either attached to a fluorophore for use in sensing applications and/or attached to a solid support to create affinity resins for use in protein enrichment applications. Other projects are also available, including joint projects with A/Prof Liz New