BMC3105 - Emerging Technologies in Drug Discovery

Leader: Dr Ian Crosby and Dr Don McNaughton

Offered

Parkville Second semester 2007 (Day)

Synopsis

This unit introduces the participants to a number of recently emerged, or emerging, technologies that have proven utility or have the potential to be useful in medicinal chemistry. The unit is designed to update itself by requiring at least 1/6 of the course to be changed annually and/or critically reviewed as to it being a currently emerging technology.
This years focus will be on synchrotron science and in particular the synchrotron resources that will be available on the Australian synchrotron scene.

Objectives

At the successful completion of this unit the participant will:

1. Understand how synchrotrons work and understand the properties of synchrotron light
2. Be able to describe the advantages of using synchrotron sources when compared with laboratory sources
3. Be aware of the great range of synchrotron beamlines and their primary uses
4. Have a more detailed knowledge of the beamlines that are likely to be of use to medicinal chemists
5. Have a knowledge of synchrotron applications in drug design, drug synthesis, drug analysis and drug interaction
6. Understand the general concepts of scale-up and scale-out as applied to the manufacture of fine chemicals including therapeutics
7. Have a detailed knowledge of micro-reactor technology and a working knowledge of micro-devices
8. Be familiar with the underlying principles and relative merits of scale-out versus scale-up
9. Be familiar with the design and application of micro-reactor technology in chemical production
10. Have a knowledge of alternative solvents of use in synthetic chemistry applications, specifically as applied to synthesis of drugs and drug-like molecules - advantages and disadvantages
11. Be able to describe the types of ionic liquids, as well as their synthesis and properties
12. Have a knowledge of the use of ionic liquids in synthesis
13. Be able to describe the use of supercritical CO2 in synthesis, with specific reference to controlling stereoselectivity in drug synthesis
14. Be able to describe the use of high temperature water in synthesis
15. Understand the goals of proteomics and be familiar with the various methods used to ascribe function to proteins
16. Appreciate the important role of synchrotrons in high-throughput structural genomics
17. Be familiar with the applications of genomic research findings in disease characterisation and gene therapy
18. Appreciate the role of genomics in lowering drug development costs, improving drug design and reducing death and injury due to side effects
19. Understand how the information on the drug-target interaction revealed at ultra-high resolution can be used to explain the inhibitor binding mechanism and target selectivity
20. Have a broad understanding of the various fragment-based approaches to drug discovery.
21. Understand the process of identifying and linking low affinity molecular fragments to product higher affinity ligands for a target biomolecule
22. Have a detailed knowledge of the principles and key reactions involved in dynamic combinatorial chemistry and click chemistry
23. Appreciate the scope of reactions and methods used in linking fragments in situ
24. Have a knowledge of the use of x-ray crystallography and mass spectrometry in fragment-based approaches to drug discovery
25. Be familiar with successful examples where a fragment based approach has resulted in high affinity ligands for protein targets
26. Have a good understanding of combinatorial and Parallel Synthesis in Drug

Discovery
including an appreciation of the historical perspective of combinatorial chemistry and the reasons for its evolution

27. Understand the different types of combinatorial libraries, ie "split and mix mixtures" vs discrete compounds
28. Be able to appreciate library quantity vs quality and the diversity of librariesand know how the technology can be used in lead indentification and in lead optimisation Understand the differences of solid vs solution combinatorial chemistry and appreciate time to develop solid phase synthesis chemistry and types of linkers
29. Have knowledge of the uses of solid supported reagents, scavengersand about parallel chemistry and equipment, manual vs automated systems.
30. Know about the commercial pressures as to purity and cost and their changing over time, use of lanterns in scaling up, tagging & tracking systems, automate systems, manual

systems.

Assessment

Exam: 70%; Assignment: 30%