PSC3131 - Analysis of drug-receptor interactions - 2019

The subject expands on the use of spectroscopic and spectrometric techniques and their applications in medicinal chemistry. After a review of structural elucidation via analysis of one dimensional NMR spectra, a range of more complex methods will be covered. The use of two dimensional NMR in the identification and characterisation of more complex organic compounds is introduced. Techniques for the assignment of spectra for more complex molecules will be described and the application of NMR spectroscopy to larger biomolecules including peptides will be introduced.

The energetic factors which drive the processes of drug-receptor interaction will be described and energetic factors that drive the processes of drug-receptor interactions will be discussed. The use of electronic spectroscopy, including absorption and fluorescence, for measurement of drug-protein binding will be described. The uses of other biophysical techniques including surface plasmon resonance and calorimetry will also be discussed. The use of NMR spectroscopy to measure the interaction of drugs with biological molecules and the effects of chemical and conformational exchange on the appearance and analysis of NMR spectra will be described.

This will involve:

• thermodynamics
• advanced NMR Spectroscopy
• biophysical techniques for measurement of interactions
• optical Spectroscopy.

After completing this unit students will be expected to be able to:

1. Analyse and interpret two dimensional spectra so as to identify the chemical structures of compounds;
2. Define the term Nuclear Overhauser Enhancement (NOE) and account for the observation of NOEs in one-dimensional and two-dimensional NMR spectra of both small and large molecules;
3. Analyse and interpret NOE data to determine the conformation of small molecules;
4. Analyse and assign two-dimensional NMR spectra of small peptides;
5. Describe quantitatively the relationship between enthalpy, entropy and free energy;
6. Describe quantitatively the relationship between changes in free energy and equilibrium;
7. Apply the concepts of this thermodynamics module to selected examples of biochemical energetics, protein-drug binding and drug-receptor interactions;
8. Describe the principal NMR-based strategies for drug discovery and design;
9. Detail the factors which govern photon-initiated electronic excitation, and describe the processes by which molecules can relax. In particular, to describe the phenomena and applications associated with fluorescence;
10. Apply their knowledge of biophysical techniques including NMR spectroscopy, fluorescence spectroscopy, surface plasmon resonance and calorimetry to analyse experimental data describing drugs binding to their receptors
11. Measure and record data relevant to the understanding of drug structure and and drug-receptor interactions;
12. Perform numerical calculations based on experimental or theoretical data;
13. Present written or oral results of experimental work.

Final exam (2 hour): 60%; mid-semester exam: 20%; laboratory assessments: 20%.

Contact hours for on-campus students:

• Twenty four 1-hour lectures
• Twelve 1-hour applieds
• Nine 4-hour laboratories

See also Unit timetable information

http://www.monash.edu/pharm/current/