SFKKIL003U Biopharmaceuticals: Chemical Design & Modification of Biomacromolecules

Volume 2013/2014
Education
Kandidatuddannelsen i farmaci
Kandidatuddannelsen i farmaceutisk videnskab
MSc in Pharmaceutical Science
MSc in Medicinal Chemistry
Content

First, the physicochemical and pharmacological properties of macromolecules are briefly introduced, followed by the focus of the course on 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 problem excercises related to the basic elements of the course as well as student presentation and plenary discussion of selected scientific articles in order to facilitate an in-depth understanding of both theoretical and practical aspects of biopharmaceutical drug research (it is compulsory that each student as a member of a group of 2-3 students presents one article during the course).
In addition, laboratory work comprise 5 days of 4 hours referring to peptide synthesis and protein modification (preparation of lab reports is compulsory).

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

-  Peptide- and protein-based drugs, inculding modified peptides 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.

 -  Basic and some advanced principles of solid-phase peptide synthesis (incl. combinatorial and parallel approaches) and optimization.

-  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 theoretical and practical 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 theoretical and practical aspects of 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.
Literature
Selected book chapters:

Chapters (1-3, 5, 7, and 12-14) in Peptide Synthesis and Applications (Series: Method in Molecular Biology, Vol. 1047; Eds: Jensen, K.J.; Tofteng, P.S.; Pedersen, S.L.). Humana Press 2013 (Springer).

Chapter on "Chemical Biology" in Textbook of Drug Design and Discovery (CRC Press 2012; eds. Krogsgaard-Larsen, P.; Strømgaard, K.; Madsen, U.)

Chapter on "Peptide and protein derivatives" (pp. 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:

Peptidomimetics (2 reviews) 
Biologically active peptides (2 reviews)
Drug delivery vehicles (2 reviews)
Nucleic acids and analogues thereof (2 reviews)
Antibodies and Vaccines (3 reviews)

Single chapters of textbooks (already used in other courses related to biopharmaceuticals) and reviews will be available 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: 24
Class sessions: 12 (6 x problem solving; 6 x journal clubs)
Laboratory exercises: 20
Individual study report (2 weeks for preparation)
  • Category
  • Hours
  • Colloquia
  • 12
  • Exam
  • 20
  • Laboratory
  • 20
  • Lectures
  • 24
  • Preparation
  • 78
  • Project work
  • 52
  • Total
  • 206
Credit
7,5 ECTS
Type of assessment
Written assignment
Oral defence, 30 min under invigilation
Essay in the format of a scientific review (size: max. 20.000 characters including 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 2 weeks to prepare this.
This essay is to be presented during an oral defense during which questions related to the essay as well as to general subjects within the course content.
Aid
Written aids allowed
  • For the individual written assignment: all written 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.

The contents of the review paper is expected to be presented in a concise way that shows that the student has understood be principles involved and subsequently the student is expected to discuss the paper with regards to questions directly related to the subject as well as answer a few questions related to the course content in general.


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 paper 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.
The paper must be presented in a clear way that demonstrates a thorough understanding of its content. In addition the student must be capable of answering questions related to the subject exhaustively. Finally, the student is required to demonstrate a high understanding of other  principles and methods within the course in response to complementary general questions.

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.
The paper must be presented in a way that demonstrates a good understanding of its content. In addition the student must be capable of answering questions related to the subject with only minor errors. Finally, the student is required to demonstrate a  good understanding of other principles and methods within the course in response to complementary general questions.

02 - Acceptable performance: This grade is awarded for the barely acceptable essay which shows that the student only wit 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.
The paper must be presented in a way that demonstrates an understanding of the main parts of its content. In addition the student must be capable of answering questions related to the subject to a degree that shows knowledge of the most essential parts. Finally, the student is required to demonstrate an understanding of other basic principles and methods within the course in response to complementary general questions.