MRes in Organic Chemistry: Drug Discovery

DD Protein


UCL Chemistry offers a one-year MRes in Organic Chemistry focused on the drug discovery process.  The course is designed for chemistry graduates who wish to advance both their practical and theoretical skills in organic chemistry related to the drug discovery process. Students therefore take a range of taught courses including Molecular Modelling, Principles of Drug Design, Cheminformatics, Asymmetric Synthesis and Fragment Based Drug Design.  The largest component of the MRes however are two five-month research projects that each student undertakes in two different research laboratories in UCL Chemistry.  These projects are interdisciplinary in nature and involve close collaboration with leading scientists from both UCL Life Sciences and the pharmaceutical industry. This gives students an outstanding training in the processes that lead to development of early-stage drug candidates.

Background

For many years UCL has had major research and teaching interests in drug discovery and medicinal chemistry. The first undergraduate degree programme in Medicinal Chemistry in the UK was started at UCL in 1974, following discussions between Professor James Black from the Department of Pharmacology and Professor Charles Vernon from the Department of Chemistry, and is still continuing today.

Since the solution of the human genome project there has been an exponential growth in the identification of new biological targets of potential importance to human disease, many of which offer opportunities for the development of small molecule therapeutics. It is increasingly recognised that leading universities can play an important role in carrying out the early-phase drug discovery process, as well as providing the next generation of research leaders in this field.

The School of Life and Medical Sciences (incorporating the Medical School) at UCL brings together one of the world's major concentrations of biomedical researchers, with ground breaking translational work underpinned by excellence in basic science, and a depth and breadth of biomedical research which is the strongest in the UK.

Programme Structure

The course begins towards the end of September each year and finishes in September the following year.

The course structure is based on a credit system in which 15 UCL credits (equivalent to 6 ects - European credit transfer and accumulation system) comprise around 150 hours worth of study and 180 credits are required for successful completion of a masters programme. For the Drug Discovery MRes, Students take the following modules:

  • Two modules from  from the Wolfson Institute of Biomedical Research worth 15 credits each.
  • One masters-level chemistry module (Principles of Drug Design, Biological Chemistry, Stereochemical Control in Asymmetric Synthesis, Synthesis and Biosynthesis of Natural Products, Structural Methods in Modern Chemistry, Organometallic Chemistry) worth 15 credits.
  • Two transferrable skills modules (Investigating Research and Professional Development in Practice) worth 15 credits each.
  • Two research rotation projects in the Department of Chemistry submitted as a single portfolio worth 105 credits in total.

Research Projects

The following rotation projects are a selection of those available to students enrolling in 2012.  Many more projects will be available before the MRes commences in September and a full list, from which you will select two rotation projects will be sent to you when you are offered a place on the course.

Synthesis of Biologically Active Oxetanes and Azetidines - Dr Tom Sheppard

Four-membered rings are synthetically challenging targets with many potential uses in medicinal chemistry due to their rigid well-defined structure. However, their use is currently limited by the lack of available methods for the stereocontrolled synthesis of substituted derivatives. This is particularly true for highly substituted oxetanes and azetidines which are of considerable interest in a wide range of medicinal chemistry projects in the pharmaceutical industry, but are difficult to access using existing chemistry. In this project we are particularly interested in developing new synthetic routes to substituted azetidines. The introduction of an azetidine ring into a lead compound structure, in place of a piperidine ring for example, can often impart greater metabolic stability whilst maintaining high levels of activity.

Development of Tracers for Imaging of Excitatory Neurotransmission with PET and SPECT - Dr Erik Arstad

Over activation of excitatory neurotransmission can result in excessive accumulation of Ca2+ ions in neurons, leading to excitotoxicity and neuronal death. The resulting localised neuronal destruction is a central event in many acute and chronic brain disorders, including stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, multiple sclerosis and epilepsy. Development of tracers for imaging of excitatory neurotransmission with positron emission tomography (PET) and single photon emission computed tomography (SPECT) may therefore enable early detection of neurodegenerative diseases, and would be of tremendous value for drug development. We propose to develop state-dependent ion channel radioligands for imaging of excitatory neurotransmission.

Anti-Cancer Therapeutics and a new Pro-Drug Strategy - Dr Jamie Baker

This project has two aims; 1) The design and synthesis of stabilised analogues of the peptide hormone somatostatin. Such analogues are widely sought for many clinical applications, including cancer treatment, due to the instability of somatostatin itselfin vivo. 2) The development of a new pro-drug strategy. Pro-drugs are extremely important in cutting-edge drug-development (such as magic-bullet therapy) as they prevent many undesired side effects and maximise efficacy.

Chemical Screen for Activators of Epicardium-Derived Progenitor Cells in Cardiac Repair and Regeneration - Professor Steve Caddick

We propose a phenotypic chemical screen using an in-house UCL Chemistry small molecule library for activators of a recently described population of adult epicardium-derived progenitor cells (EPDCs). EPDCs have the potential to contribute de novo blood vessels and cardiac muscle in the setting of ischaemic heart disease and myocardial infarction (“heart attack”). High throughput epicardial explants will be screened with small molecules against end points of cellular migration, proliferation and differentiation and further assessed for quantitative structure activity relationships. Affinity purification assays will be used to implicate candidate molecules with known functional biochemical signalling pathways in terms of EPDC phenotype and cell fate.

Small Molecule Annexin Probes: In Silico Design, Synthesis and Annexin Specificity - Professor Helen Hailes

Annexins are Ca2+ and phospholipid binding proteins, expressed in both animals and plants, that are characterised by a highly α-helical and tightly packed protein core domain. The structures of many annexins have been elucidated and the biological function of several annexins is now understood. The challenge now is to identify small novel molecules for applications such as therapeutics, or as molecular probes with high affinity and specificity to individual annexins such as annexin 2, over other related proteins. By inhibiting the interactions between annexin 2 and its various ligands these would have potential uses in clinical (prostate) cancer treatments and as research tools to study annexin function in cell culture models.

Novel Antagonists of the Human Histamine H4 Receptor to Counter Itch and Inflammatory Diseases - Professor Charles Marson

The aim of this project is to synthesise, validate and patent a novel class of antagonists of the human histamine H4 receptor and to evaluate them as agents to diminish pruritus (itch).

Development of Nitroimidazole MRI Contrasting Agents for the Investigation of Hypoxia - Dr Mike Porter

Despite the clinical importance of hypoxia and ischaemia, there arecurrently no effective methods for imaging hypoxic tissues in vivo. Thisproject aims to develop new hypoxia-selective MRI contrast agents bycoupling 2-nitroimidazole ? a motif which is known to bind to hypoxic cells? with contrast agents based on gadolinium(III) and stable organic freeradicals. The agent will be assessed and refined in collaboration withcolleagues in medical research: an effective agent would be adopted inmedical practice worldwide.

Development of Selective Inhibitors of Cathepsin D and Cathepsin E - Dr Alethea Tabor

Antigen processing generally involves uptake of proteins into antigen presenting cells. These proteins are then cleaved into smaller fragments by a variety of protease enzymes to give small peptide fragments, which are then displayed on the cell surface and trigger the immune response. Understanding how this process works is crucial to developing new therapeutic approaches for autoimmune diseases. In this project we will develop a series of selective inhibitors of the aspartic protease cathepsin E, based on a newly isolated natural product, grassystatin C. We have previously shown that this enzyme has a non-redundant role in antigen processing. In contrast, the closely related proteinases cathepsin D plays an important role in regulated cell death (apoptosis) and hence in the resolution of inflammation. In order to interfere with cathepsin E activity for either experimental or therapeutic purposes, it is therefore essential to have inhibitors able to distinguish between these two enzymes.

Synthesis of Novel Peptidomimetics for the Treatment of Osteoperosis - Dr Jon Wilden

Current treatment for rheumatoid arthritis and osteoporosis are in need of significant improvement, in particular, due to concerns arising from the major class of anti-osteoporotic drugs, the bisphosphonates. This project seeks to exploit a novel observation made in the Henderson laboratory, that a heat-shock protein (HSP60) isolated from the bacterium that causes tuberculosis is a very effective inhibitor of osteoclast formation (osteoclasts being one the bone cells responsible for naturally degrading bone and a cell implicated in the pathogenesis of osteoporosis and rheumatoid arthritis). Synthetic peptide and truncation mutagenesis studies have identified the sequence 460-491 as being responsible for the osteoclast inhibitory activity. This project will focus on the synthesis of short peptides and peptidomimetics that have been identified from HSP60 as being responsible for this protein's osteoclast inhibitory activity.

Identification of Small Molecule Inhibitors of hFis1, a Mitochondrial Fission Protein as a Novel Therapeutic Strategy for Acute Myocardial Infarction - Professor David Selwood

The overall aim of the project is to identify a small molecule inhibitor of the mitochondrial fission protein, hFis1. This inhibitor would be a prototype novel therapeutic agent for reducing myocardial ischaemia-reperfusion injury, which will benefit patients with coronary heart disease.

How to Apply

Information on the application procedure is included below.

Eligibility

Qualifications

In general, applicants should hold a good honours degree (i.e. equivalent to at least a second class honours degree at a British University) in chemistry or in a related subject. 

Other applicants will be considered if they have relevant postgraduate experience in a science related field. The MSc in Drug Discovery Course Organiser, Dr Jon Wilden, will advise on this matter. 

The UCL pages containing advice for international students can be found on the UCL international students page.

Fees and Funding

The fees for the MRes in Organic Chemistry: Drug Discovery are £7,500 (UK Students) and £20,250 (Overseas Students).

UCL offers some scholarships for graduate studies, the details of which can be found on the UCL scholarships page.

Application Procedure

Applications are now open for the 2013 entry for the MRes Programme.  Candidates are encouraged to apply online if possible.  To apply online click here and select MRes in Organic Chemistry: Drug Discovery from the list.

If you are unable to apply online for any reason, please contact the postgraduate admissions secretary who will arrange for you to submit a hard-copy application.

Deadline for Application

The deadline for applications is the end of August 2013.

Further Information

Information on all aspects of studying at UCL as a postgraduate can be found on the UCL graduate study page and information specifically for international students thinking of studying at UCL can be found UCL international students page.

For any further information regarding the MRes in Organic Chemistry: Drug Discovery, please contact the programme director by completing the following form, outlining your request using the Additional Information box.

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