SFAK20010U Medicinal and Biostructural Chemistry

Volume 2020/2021
Education

MSc Programme in Pharmacy and Pharmaceutical Sciences (danish programmes cand.pharm and cand.scient.pharm) - compulsory

MSc Programme in Medicinal Chemistry - compulsory

MSc Programme in Pharmaceutical Sciences (english programme) - compulsory

Content

The course deals with the most important principles of drug design and discovery of small molecules and biopharmaceuticals, including fundamental aspects of 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 basic knowledge about the structure of proteins, including 3-D structural information and experimental methods for structure determination. Methods for design and development of substances - small molecules and biopharmaceuticals, in particular - with specific or selective effect on biochemical or physiological processes will be introduced. Emphasis will be on the significance of steric, stereo chemical, conformational and electrostatic factors for decision making in 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, and particular emphasis is on peptides and proteins as drugs, including peptidomimetics and peptide and protein design. 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

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 small molecule or biopharmaceutical drugs with macromolecules in the organism. This includes a basic 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.

At the end of the course, students are expected to be able to:

 

Knowledge

  • Define the concepts used to describe molecular interactions in the context of drug design and discovery
  • Explain the principles of small molecules and biopharmaceutical drug actions on a number of biological targets
  • Define the basic concepts from bioinformatics used in drug design and discovery
  • Understand, reflect, explain and critically evaluate molecular interactions in the context of drug design and discovery
  • Understand, reflect, explain and critically evaluate the principles of drug actions on a number of biological targets
  • Understand, reflect and critically evaluate results from bioinformatics in drug design and discovery

 

Skills 

  • Master, discuss and evaluate the use of 3D-structures in ligand design
  • Master, discuss and evaluate the use of the information available from sequenced genomes to solve problems related to drug design and discovery
  • Master, discuss and evaluate the use of pharmacophores in drug design
  • Master, discuss and evaluate the use of basic methodologies of receptor pharmacology in drug design
  • Discuss and evaluate fundamental principles of peptide and protein design
  • Assess, evaluate, independently discuss and present published research related to drug design and discovery.

 

Competences

  • Independently plan and prepare presentations of published research
  • Implement the use of the relationship between chemical structure and biological activity of important drug classes
  • Take responsibility for and coordinate presentations of published research related to drug design and discovery
  • Implement and develop further the use of 3D structures in ligand design
  • Implement and develop further the use of the relationship between chemical structure and biological activity of important drug classes

  • Textbook of Drug Design and Discovery, Povl Krogsgaard-Larsen, Kristian Strømgaard, Ulf Madsen (Eds.), 5th Edition, 2016, 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 basic 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.
•31 lectures (45-minutes)
•10 class lessons as journal clubs (45-minutes)
•4 Four hour computer exercises
  • Category
  • Hours
  • Lectures
  • 31
  • Class Instruction
  • 10
  • Preparation
  • 101
  • Theory exercises
  • 16
  • Guidance
  • 48
  • Total
  • 206
Continuous feedback during the course of the semester

Feedback is given to student presentations in class hours, which are in a 'journal club' format.

Credit
2,5 ECTS
Type of assessment
Continuous assessment
In order to obtain the course certificate the student should participate actively during class lessons and computer practical exercises. Additionally, upload of completed quizzes are required.
Marking scale
passed/not passed
Censorship form
No external censorship
Criteria for exam assesment

To achieve a course certificate the student must be able to:

 

Knowledge

  • Define the concepts used to describe molecular interactions in the context of drug design and discovery
  • Explain the principles of drug actions on a number of biological targets
  • Define the basic concepts from bioinformatics used in drug design and discovery
  • Understand, reflect, explain and critically evaluate molecular interactions in the context of drug design and discovery
  • Understand, reflect, explain and critically evaluate the principles of drug actions on a number of biological targets
  • Understand, reflect and critically evaluate results from bioinformatics in drug design and discovery

 

Skills 

  • Master, discuss and evaluate the use of 3D-structures in ligand design
  • Master, discuss and evaluate the use of the information available from sequenced genomes to solve problems related to drug design and discovery
  • Master, discuss and evaluate the use of pharmacophores in drug design
  • Master, discuss and evaluate the use of basic methodologies of receptor pharmacology in drug design
  • Discuss and evaluate fundamental principles of peptide and protein design
  • Assess, evaluate, independently discuss and present published research related to drug design and discovery.

 

Competences

  • Independently plan and prepare presentations of published research
  • Implement the use of the relationship between chemical structure and biological activity of important drug classes
  • Take responsibility for and coordinate presentations of published research related to drug design and discovery
  • Implement and develop further the use of 3D structures in ligand design
  • Implement and develop further the use of the relationship between chemical structure and biological activity of important drug classes

 

Credit
5 ECTS
Type of assessment
Written examination, 3 hours under invigilation
Individual 3-hour written examination.
Examination design:
The examination assignment typically consist of 3 assignments each with 5 sub-assignments. For each sub-assignment at least 3 possible answers are provided in a multiple choice format. Typically one of the 3 assignments deal with biostructural aspects, whereas the remaining two assignments are more medicinal chemistry focused.
Aid
Written aids allowed

There is access to the following at the exam on Peter Bangs Vej:

  • R – Statistical programme
  • MathType - formel programme
  • Maple
  • Digital Notes (It is allowed to upload notes for the ITX exam via digital exam. You will find a link to this feature from your exam in Digital Exam)
  • USB allowed

 

Students are allowed to bring a molecular model building set.

Marking scale
7-point grading scale
Censorship form
No external censorship
Criteria for exam assesment

To achieve the grade 12 the student must have:

 

Knowledge

  • Define the concepts used to describe molecular interactions in the context of drug design and discovery
  • Explain the principles of drug actions on a number of biological targets
  • Define the basic concepts from bioinformatics used in drug design and discovery
  • Understand, reflect, explain and critically evaluate molecular interactions in the context of drug design and discovery
  • Understand, reflect, explain and critically evaluate the principles of drug actions on a number of biological targets
  • Understand, reflect and critically evaluate results from bioinformatics in drug design and discovery

 

Skills 

  • Master, discuss and evaluate the use of 3D-structures in ligand design
  • Master, discuss and evaluate the use of the information available from sequenced genomes to solve problems related to drug design and discovery
  • Master, discuss and evaluate the use of pharmacophores in drug design
  • Master, discuss and evaluate the use of basic methodologies of receptor pharmacology in drug design
  • Discuss and evaluate fundamental principles of peptide and protein design
  • Assess, evaluate, independently discuss and present published research related to drug design and discovery.

 

Competences

  • Independently plan and prepare presentations of published research
  • Implement the use of the relationship between chemical structure and biological activity of important drug classes
  • Take responsibility for and coordinate presentations of published research related to drug design and discovery
  • Implement and develop further the use of 3D structures in ligand design
  • Implement and develop further the use of the relationship between chemical structure and biological activity of important drug classes