SFAKM0011U Medicinal and Biostructural Chemistry

Volume 2013/2014
Education
MSc in Pharmaceutical Sciences - compulsory, MSc in Medicinal Chemistry - compulsory, Cand.Scient.Pharm. - compulsory, Cand.Pharm. - compulsory
Content
The course will deal with the most important principles of drug design and discovery, bioinformatics and structural biology. Genome structure will be introduced focusing primarily on the importance of systematic variations of the human genome in relation to diseases. Sequence alignment will be discussed and students will get to use internet based tools for sequence analyses. The course will give basis knowledge about the structure of proteins, including 3-D structural information and experimental methods for structure determination. Methods for design and development of substances with specific or selective effect on biochemical or physiological processes will be introduced. Emphasis will be on the significance of steric, stereochemical, conformational and electrostatic factors for drug design. The importance of changes of structural and physico-chemical parameters in order to obtain drugs with appropriate pharmacokinetic properties will be discussed. The importance of the prodrug principle for improving the pharmacokinetic properties of drugs will also be addressed. Students will be introduced to systems biology and the importance of protein-protein interactions. Certain aspects of chemotherapeutic and antiviral substances will be covered, with emphasis on the chemical and structural factors crucial to the activity of these substances. Enzyme structure and the concept of enzyme inhibitors will also be dealt with and discussed in relation to developing drugs with anti-carcinogenic or anti-viral effects. Ion channels as the pharmacological and therapeutic point of intervention and compounds with direct impact on specific ion channels will be introduced. The course will place considerable emphasis on the study of structure-activity relationships in certain groups of drugs. Some groups of psychotropic drugs, hypnotics and immunomodulating agents will be studied. In general, course teaching will concentrate on the structural factors relative to the effect of certain drugs. Central neurotransmitter systems and research in drug design on these systems will be mentioned. The pharmacokinetic aspects related to the passage of the blood-brain barrier will be highlighted. Course teaching will relate primarily to the organo-chemical aspects of drug activity and development, but will also cover bio-inorganic chemistry topics. These last topics will focus on the role of metal ions in biochemical processes and their importance for the biological effect of certain metal-binding substances. Students will study the selective removal of toxic metal ions from the organism by the forming of chelates with various organic compounds.
Learning Outcome

Formål / Objective

The course objective is to give students insight into the molecular mechanisms of action of selected drugs and to acquaint them with the fundamental principles of drug design and discovery. The course aims to expand students knowledge of the chemical and structural factors relating to the main drug groups and to give examples of the use of chemical principles to clarify the interaction of drugs with macromolecules in the organism. This includes a basal understanding of the 3-D structure of drugs and target macromolecules. Students shall be able to use the vast amount of sequence and biostructural information on relevant target macromolecules available on internet databases, and to use such information about proteins primary sequences and 3-D structures of macromolecules in the context of drug design.

Målbeskrivelse / Course outcome

  • To be able to account for the relationship between chemical structure and biological activity of important drug classes
  • To be able to account for the key principles applied when designing and developing new drugs on a rational basis
  • To be able to account for the key chemical, physico-chemical and pharmacokinetic properties of the main drug groups
  • To be able to use 3D-structures in ligand and inhibitor design
  • To be able to use the information available on the internet from sequenced genomes to solve problems related to drug design and development
  • To be able to use basic knowledge about conformation of small molecules, stereochemistry, pKa-values, ionization and electrostatic ligand-macromolecule interactions in the discussion in the mechanisms of action of drugs at the molecular level.
Literature
  • Textbook of Drug Design and Discovery, Povl Krogsgaard-Larsen, Kristian Strømgaard, Ulf Madsen (Eds.), 4th Edition, 2010, CRC Press
  • Practical Bioinformatics. Michael Agostino, Garland Science, Taylor and Francis Group, LLC, 2013. ISBN: 978-0-8153-4456-8.
  • Biochemistry. Jeremy M. Berg, John L. Tymoczo and Lubert Stryer, 7th edition, 2011
  • Four scientific papers available at the course website
Course teaching is based on the assumption that students have previous knowledge from basal courses in organic chemistry, physical chemistry, biochemistry and general pharmacology, preferably corresponding to the content of the compulsory courses on these topics in the BSc in Pharmacy programme. Special IT knowledge is not a requirement, but all students need to bring a laptop computer for the computer exercises.
•32 lectures (45-minutes)
•10 class lessons (45-minutes)
•four 4-hour computer exercise
NB! Schedule for block 1 is found here: https:/​/​skema.ku.dk/​sund1314/​dk/​module.htm
  • Category
  • Hours
  • Colloquia
  • 10
  • Guidance
  • 48
  • Lectures
  • 32
  • Preparation
  • 100
  • Theory exercises
  • 16
  • Total
  • 206
Credit
7,5 ECTS
Type of assessment
Written examination, 3 timer under invigilation
Prøveform / Examination type:
Individual 3-hour written examination.

Prøvedesign / Examination design
The examination assignment typically consist of 3 assignments each with 6-7 sub-assignments. Typically one of the 3 assignments deal with biostructural aspects, whereas the remaining two assignments are more medicinal chemistry focused.

Særlige forhold / Special conditions:
Prerequisites:•Actice participation in the computer practical exercises. Validated through upload of completed quizzes.
•Active participation in class lessons.
Aid
Only certain aids allowed
All written materials, approved pocket calculator and molecular model building set.
Marking scale
7-point grading scale
Censorship form
External censorship
Re-exam
Re re-exam (resit) after block 2. Please note that the registration period for participation in the re-exam (resit) is different from the registration period stipulated in the general curriculum provisions. The exact registration period can be found in the exam timetable.
Criteria for exam assesment

Beskrivelse af prøven og bedømmelse / Description of examination and assessment criteria

Beståkrav / Pass criteria

See description under grade 02 below.

Karakterbeskrivelse / Description of grades

12 - Excellent performance
Mastery of the items mentioned under course outcome.7 - Good performance
A good level of understanding and knowledge of the items mentioned under course outcome.02 - Acceptable performance
A reasonable level of understanding and knowledge of the items mentioned under course outcome