At the end of the course, the student should have acquired knowledge of the main applications of enzymes in the discovery and production of drugs. He/she should be able to critically analyze the structure-activity relationships of enzyme inhibitors by evaluating whether the assay conditions used are appropriate for the type of inhibitor analyzed. He/she should also be able to assess the impact of the choice of the expression system on the properties of the recombinant enzymes used in substitution therapy. Finally, he/she should have learnt the general principles of the application of enzymes in the stereoselective synthesis of organic molecules.
1. Knowledge and understanding. At the end of the course the student is expected to be able to:
- Know and understand the main mechanisms of enzymatic inhibition
- Describe the main inhibition essays
- Know the main expression systems for the production of recombinant enzymes used in therapy
- Know the main applications of enzymes in drug production
2. Applied knowledge and understanding. At the end of the course the student is expected to be able to:
- Explain the fundamental criteria for the development of an enzyme inhibition assay
- Identify the best expression system for an enzyme depending on the organism of origin and the therapeutic use
3. Communication skills. At the end of the course the student is expected to be able to:
- communicate the topics in a clear, concise and effective way.
4. Ability to learn. At the end of the course the student is expected to be able to:
- make connections between the various topics learned
- understand the potential of enzymological research
Knowledge of Biochemistry, Applied Biochemistry and Organic Chemistry.
Course contents summary
The course will cover all the relevant aspects of enzymes’ exploitation in drug discovery, production, and development. The course is divided into three blocks:
- enzymes as targets
- enzymes as drugs
- the exploitation of enzymes in green chemistry with special focus on drug synthesis
The course aims at providing the student with useful tools to understand the mechanism of action of enzymes, which will help in critically interpret the structure-activity data for enzymatic inhibitors and in understanding the application of enzymes in replacement therapy and in chemical synthesis.
ENZYMES AS TARGETS
- development of enzymatic assays for inhibitors
- determination and relevance of the mechanism of inhibition
- IC50 and Ki. Cheng-Prusoff's equation
- Set-up of a HTS for inhibitors identification
- examples from literature
ENZYMES AS DRUGS
- overview of enzymes in the replacement therapy
- the importance of expression host in proteins targeting and pharmacokinetics of recombinant drugs
- the use of enzymes in the therapy of lysosomal accumulation diseases
ENZYMES IN DRUG SYNTHESIS
- overview of the exploitation of enzymes in green chemistry
- enzyme evolution for industrial applications
- relevant examples of enzyme application in drug synthesis
Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists, 2nd Edition (2013). Robert A. Copeland. Wiley. ISBN: 978-1-118-48813-3
Scientific papers suggested by the teacher.
The teaching activities will be carried out in the form of in-person lectures. Alternative online lectures will depend on decisions from the University.
Assessment methods and criteria
The exam is oral and will be carried out in person, if allowed by the regulations for the containment of the Covid-19 pandemic.
Questions will cover the entire program. The use of the appropriate scientific language and the autonomy in the discussion will be evaluated along with the knowledge of the topics covered by the program.