Chemical Biology in Drug Discovery Laboratory
Lab head: Rachel Codd
Location: Blackburn Building, Camperdown
Our laboratory applies techniques in chemical biology to drug design, discovery, and pharmaceutics processing. Our chief interests lie in better understanding the mechanisms used by bacteria to acquire iron, from the level of siderophores, which are small-molecular-weight compounds produced by bacteria to sequester Fe(III), through to the cognate Fe(III)-siderophore recognition proteins, which are expressed at the bacterial cell surface. Bacterial iron uptake is significant in biomedicine, since:
- natural siderophores or siderophore mimics can be used to treat iron-overload disease and cancer; and
- molecules that antagonise iron uptake in both pathogenic and non-pathogenic bacteria are potential antibiotics.
To access these target molecules, and to discover new bacterial metabolites of biomedical interest, our laboratory uses approaches that traverse chemical proteomics, affinity chromatography using designer resins, metal-templated synthesis, semisynthesis and precursor directed biosynthesis.
Lab members: R Codd (head)
Structure-activity relationships of desferrioxamine B conjugates
Primary supervisor: Rachel Codd
Desferrioxamine B (DFOB) is used in the treatment of β-thalassemia to ‘mop up’ excess Fe(III), which accumulates in patients as a result of their receiving frequent blood transfusions. We have made simple modifications to the structure of DFOB to produce new compounds that have shown improved toxicity and cellular Fe mobilisation measures, compared to DFOB itself. We are now interested in gaining a molecular level understanding of the stability of the new compounds in biological matrices. In this project, you will prepare derivatives of DFOB, which vary in the number of amide groups and/or hydroxamic acid groups in the linear chain region and examine the stability of the compounds in plasma and artificial gastric juice.