SFKKIL003U Biopharmaceuticals: Design & Modification of Biomacromolecules

Volume 2014/2015
Education
Kandidatuddannelsen i farmaci
Kandidatuddannelsen i farmaceutisk videnskab
MSc in Pharmaceutical Science
MSc in Medicinal Chemistry
Content

Besides an introduction to the concepts and methods that are relevant for investigating and understanding the physicochemical and pharmacological properties of macromolecules the course focus on the design, discovery and applicability of biopharmaceutical drugs, primarily those based on peptides or proteins.
Furthermore, this course will form the basis for studies on optimization of pharmaceutical properties of peptides, proteins and nucleic acids in relation to preclinial and clinical drug development. Finally, drug leads derived from these classes of macromolecules (e.g. peptidomimetics, oligonucleotide analogues and oligosaccharides) as well as relevant delivery vehicles will be discussed.
These subjects will be introduced via lectures (based on book chapters and comprehensive reviews), while the class sessions will comprise student presentations and discussion of selected scientific articles in order to facilitate an in-depth understanding of both theoretical and practical aspects of biopharmaceutical drug research. In addition, some class sessions will comprise execises on the basic elements of the course (e.g. peptide synthesis and protein modification).

The most relevant compound classes and their applications are briefly outlined below:

-  Peptide- and protein-based drugs, inculding modified peptide and proteins (primary content of the course).

-  Peptide-based delivery vehicles for biopharmaceuticals.

-  Oligonucleotides for gene therapy and antisense siRNA as putative biopharmaceutical drugs.

-  Antibodies and vaccines (including oligosaccharides as potential vaccines).


Methods and concepts:

-  Importance of structure for pharmacological activity and suitable drug properties: charge, solubility and stability, primary sequence and folding into secondary and tertiary structures (determination of these by NMR and CD spectroscopy).

 -  Basic principles of solid-phase peptide synthesis (incl. combinatorial and parallel approaches) and optimization (incl. phage display methodologies and on-resin assays).

-  Protein biosynthesis and modification: post-translational and chemical transformations (incl. analysis of these by mass spectrometry).

 - Genetic and protein engineering as a discovery and production tool for biological protein and peptide expression and modification.

Learning Outcome

Objectives
The purpose of this course is to provide students with theoretical knowledge on biopharmaceutical drug discovery as a central part of contemporary and future interdisciplinary drug discovery efforts in academia as well as in the biotech and pharmaceutical industry. The focus will primarily be on peptides and proteins as they currently constitute the most important class of biopharmaceuticals.
An additional aim is to introduce students to methodologies related to chemical synthesis, biological expression, and modification of biopharmaceuticals with a focus on their applications in drug discovery (and development).

Course outcome
At the end of the course the student is expected to have gained an understanding of the steps involved in biopharmaceutical drug discovery. Specifically the student will have acquired the competencies listed below:

- An understanding of aspects of chemical peptide synthesis relevant for biopharmaceutical drug discovery

- Capability to assess the implications of peptide/protein sequence on their folding into secondary/tertiary structure

- To read and discuss research examples concerning optimization of biologically active peptide drug leads with respect to pharmacological properties including bioavailability and in vitro cytotoxicity

- An understanding of post-translational peptide/protein modifications

- An understanding of methods used in chemical protein modification

- An understanding of the concept of unnatural mutagenesis

- Capability to understand the basic theory of protein engineering and expression of protein biopharmaceuticals 

- Basic knowledge on potential novel types of biopharmaceuticals comprising nucleic acids (and analogs thereof) and oligosaccharides in sufficient detail to follow future scientific development in this field

- Capability to search and read relevant literature and use this knowledge in biopharmaceutical research projects.
Selected book chapters:

Textbook of Drug Design and Discovery (CRC Press; eds. P. Krogsgaard-Larsen K. Strømgaard, U. Madsen)

Introduction to Peptides and Proteins (CRS Press 2010; eds. Ü. Langel et al.)

Pharmaceutical Formulation Development of Peptides and Proteins (CRC Press 2012; eds. L. Hovgaard, S. Frøkjær, M. van de Weert) 

Peptide and protein derivatives (p. 131-148), in Pharmaceutical Formulation Development of Peptides and Proteins (Taylor & Francis 2012; eds. M. van de Weert, S. Frøkjær & L. Hovgaard)


Supplementary reviews and research papers covering the following topics:

Examples of subclasses of potential drug leads (peptides, peptidomimetics and proteins), known biopharmaceuticals (e.g. peptide hormones, cytokines, antibodies etc, nucleic acids and analogues thereof, and antigens for vaccines), and drug delivery vehicles.

All teaching materials will either be part of textbooks already used in other courses related to biopharmaceuticals, or it will be available via the course homepage or as handout material.

Enrolment requires a bachelor degree (or equivalent qualifications) within the pharmaceutical, natural or medical sciences. Furthermore, basic knowledge in organic and bioorganic chemistry and molecular biology is a prerequisite.
Lectures: 16
Class sessions: 24

Individual study report (3 weeks for preparation)
  • Category
  • Hours
  • Colloquia
  • 24
  • Exam
  • 61
  • Lectures
  • 16
  • Preparation
  • 86
  • Project work
  • 20
  • Total
  • 207
Credit
7,5 ECTS
Type of assessment
Written assignment
Written examination, 1 hour under invigilation
Individual written assignment (essay) in the format of a scientific review (size: max. 25.000 characters inluding spaces; supporting figures allowed) based on literature studies on a subject agreed upon with one of the teachers and approved with the course director(s). The student will have 3 weeks to prepare this, and it will contribute 75% to the total grading of the student performance.

Multiple-choice test with approx. 25-30 statements to which the student has to decide whether they are true or false. The result of this will contribute 25% to the final grading.
Aid
  • For the individual written assignment: all written aids are allowed
    For the multiple-choice test: no aids are allowed
Marking scale
7-point grading scale
Censorship form
No external censorship
Exam period
last week of block 4
Re-exam
week 33-34
Criteria for exam assesment
For the written assigment: the review paper must reflect that the student has searched the literature, and read and understood relevant articles in order to present a state-of-the art background. Also, the student should be able to discuss and illustrate how a specific type of biopharmaceuticals may be discovered via synthesis/expression of leads that undergo optimization using appropriate methodologies.

In the multiple-choice test :
-  A correct answer results in: +1 point
-  A wrong answer results in:   -1 point 
-  A blank answer results in:    0 points


Description of grades for essay

12 - Excellent performance: This grade is awarded for the excellent essay which shows that the student in an independent way has been able to compose the essay appropriately and identify literature that covers the selected topic comprehensively.
Also, it must be obvious that the student has understood all the involved concepts and methods to such a degree that both the background and discussion of the subject has been presented in an exhaustive way without any significant shortcomings. 

7 - Good performance: This grade is awarded for the well acceptable essay which shows that the student has been able compose the essay and identify literature that covers all basic aspects of the selected topic.
Also, it should be evident that the student has understood all basic concepts and methods to such a degree that background and discussion of the subject has been presented in a clear way with only few minor shortcomings.

02 - Acceptable performance: This grade is awarded for the barely acceptable essay which shows that the student only with extensive advice has been able compose the essay and identify literature that covers most basic aspects of the selected topic.
Also, it is clear that that the student has understood most basic concepts and methods to a degree that merely allowed the background and discussion of the subject to be presented with significant lack of clarity and with several shortcomings.


Description of grades for multiple-choice exam

12 - 90-100% of maximum score

7-  65-80% of maximum score

02 -   45-55% of maximum score


The final grade will be given according to the weighed sum of the two grades for assignment (75%) and multiple-choice test (25%). In order to pass the exam the student should have obtained at least 02 in the written assignment as well as in the multiple-choice exam.

Retningslinier for forbedring af delkarakter:
  • er delkarakteren opnået i litteraturprojektet mindre end 02 skal litteraturprojektet tages om
  • er delkarakteren opnået i multiple choice eksamenen mindre end 02 skal multiple choice eksamen tages om
  • en delkarakter kan højst være gældende i 5 år. Herefter skal hele kurset tages om. Institut for Lægemiddeldesign og Farmakologi er ansvarlig for opbevaring af alle delkarakterer i 5 år.