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Medicinal Chemistry
Cursusdoel
Aims |
After this course, the student understands the concepts of medicinal chemistry and can apply this understanding to solve real problems, by designing a drug candidate based on target structure.
Assessment
The presentations about disease will be assessed by both teachers and make up 10% of the final grade (learning aims 1 and 2).
The target pitch makes up 20% of the grade (learning aim 3).
Medicinal Chemistry 6
The physicochemical properties fact sheet makes up 20% of the grade (learning aims 4 and 6).
The synthesis proposal makes up 10% of the grade (learning aim 8).
The drug design report and proposed drug candidate make up 40% of the grade (learning aims 5, 7, 9 and 10).
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Vakinhoudelijk
Every student starts an individual design project. Find a disease, that poses an obvious medicinal need, and present this in class. Select a druggable target and write a pitch to defend this choice, as if to persuade the “company” board. Select a lead compound and predict the pharmacokinetic properties of the lead, based on the physicochemical properties and hand in these properties on a fact sheet. Optimise the affinity and selectivity of the lead using structure-based design software. Propose a synthetic route for the optimised drug candidate and let it be checked by an expert. Write a report of the entire design project. The concepts of organic chemistry, biochemistry, pharmacology and medicinal chemistry that form the foundation of structure-based drug design, are taught in a just-in-time fashion. An online book is available as well. The following course components are used to reach the learning aims. - Workshops Workshops will be given just-in-time on the following topics: • Organic chemistry and functional groups • Physicochemical properties • Pharmacokinetics and pharmacodynamics • Receptor protein structure • Ligand receptor interaction • Ligand synthesis - Disease presentation Every student selects a disease, that can be considered an unmet medical need. You are asked to present information about this disease orally in 15 minutes (+5 minutes for questions). Discuss the symptoms, the prevalence, the pathophysiology (at molecular level), and current treatment. The presentation will be graded. Some tips for short presentations are given in appendix 2.1. Since the disease is the starting point for the structure-based drug design project, check in PubMed if the disease is mentioned in connection with words like novel, structure-based design, inhibitors etc. Selecting a disease with no known protein structures is a no-go. - Lectures Three guest lectures about research will be given by three principal investigators. - Target selection proposal After the presentation of the disease, the students select a target and hand in two A4 pages, explaining why they chose that target. Most relevant information can be found in the publication that is linked to the rcsb.org entry. - Predicting lead properties A lead compound should be selected and its physicochemical properties should be found/computed in order to predict its pharmacokinetic properties. This fact sheet should be handed in. - Design project Then the structure-based drug design starts. This involves selecting 3D structure of a target, making a lead compound, optimising this lead for improved pharmacodynamics (100-fold affinity enhancement, selectivity) by molecular docking, while also predicting pharmacokinetics. A synthesis route should be proposed for the final drug candidate. Write a scientific article of your drug design aimed at the disease, with an introduction, a method section, results and a conclusion/discussion. The target selection pitch can be incorporated in the report. The report should discuss disease epidemiology and pathophysiology, target structure and validation, lead optimisation for affinity and selectivity, physicochemical properties for absorption and maybe CNS penetration, and a synthetic strategy for the drug candidate. Intermediate molecules and their properties can be listed in an appendix. |
Werkvormen
Toetsing
Writing Report
Verplicht | Weging 40% | ECTS 3
Target Pitch
Verplicht | Weging 20% | ECTS 1,5
Physicochemical Properties Fact Sheets
Verplicht | Weging 20% | ECTS 1,5
Synthesis Proposal
Verplicht | Weging 10% | ECTS 0,75
Presentation
Verplicht | Weging 10% | ECTS 0,75
*midterm FEEDBACK*
Niet verplicht
Ingangseisen en voorkennis
Ingangseisen
Er moet voldaan zijn aan minimaal één van de cursussen:
Voorkennis
Er is geen informatie over ingangseisen bekend.
Voertalen
- Engels
Cursusmomenten
Gerelateerde studies
Tentamens
Er is geen tentamenrooster beschikbaar voor deze cursus
Verplicht materiaal
Er is geen informatie over de verplichte literatuur bekend
Aanbevolen materiaal
Materiaal | Omschrijving |
---|---|
BOEK | Gerhard Klebe, ‘Drug Design. Methodology, Concepts, and Mode-of-Action’, Springer, 2013. ISBN 978-3-642-17906-8. Ebook available via the library at https://link.springer.com/referencework/10.1007%2F978-3-642-17907-5. |
BOEK | Books on Organic Chemistry and Biochemistry are recommended as well. |
Coördinator
dr. E.E. Moret | e.e.moret@uu.nl |
Docenten
dr. E.E. Moret | e.e.moret@uu.nl |
dr. ir. D.T.S. Rijkers | D.T.S.Rijkers@uu.nl |
Inschrijving
Naar OSIRIS-inschrijvingen
Permanente link naar de cursuspagina
Laat in de Cursus-Catalogus zien