Biopharmaceuticals: Design and Modification of Biomacromolecules

Course 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 focuses 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) will be discussed.

These subjects will be introduced via lectures (based on comprehensive reviews and primary research articles), 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 theoretical execises on the basic elements of the course (e.g. peptide synthesis and protein modification). Also, the course comprises practical exercises in peptide synthesis and biochemical assay performance in the laboratory. These exercises illustrate basic solid-phase peptide synthesis (SPPS) methodology and biochemical evaluation of enzyme activity. For each excercise a laboratory notebook should be kept in order to facilitate writing a mandatory group report, which also includes interpretation and discussion of the achieved results (Yield, LC-MS analysis, and Michaels-Menten parameters).


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).
  • Introduction to antibodies and therapeutic relevance.
  • Introduction to oligonucleotides for gene therapy and antisense siRNA as putative biopharmaceutical drugs.
  • Introduction to vaccines.

 


Methods and concepts:

  • Importance of structure for pharmacological activity and suitable drug properties: charge, solubility, stability and delivery. 
  • Primary sequence and folding into secondary and tertiary structures and methods for manipulating these.
  • Principles of solid-phase peptide synthesis (incl. combinatorial and parallel approaches) and optimization. Advanced peptide chemistry including selection of linkers, coupling reagents and protecting groups.
  • Protein biosynthesis and modification: post-translational and chemical transformations.
  • Genetic and protein engineering as a discovery and production tool for biological protein and peptide expression and modification.
  • Practical manual solid-phase peptide synthesis and simple modification of proteins.
  • Chemical protein synthesis and semisynthesis  
Education

MSc Programme in Medicinal Chemistry - compulsory

MSc Programme in Pharmacy (Danish programme cand.pharm) - elective

MSc Programme in Pharmaceutical Sciences (Danish programme cand.scient.pharm) - restricted elective

MSc Programme in Pharmaceutical Sciences (English programme) - restricted elective

 

Learning outcome

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.

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

Knowledge

  • comprehend the steps involved in biopharmaceutical drug discovery
  • understand aspects of chemical peptide synthesis relevant for biopharmaceutical drug discovery
  • understand post-translational peptide/protein modifications
  • understand methods used in chemical peptide and protein modification
  • understand the concept of non-canonical amino acid mutagenesis
  • appreciate of the potential of novel types of biopharmaceuticals (e.g., nucleic acids and analogs thereof) in sufficient detail to follow future scientific developments

 

Skills

  • search and read relevant literature and use this knowledge in biopharmaceutical research projects.
  • perform solid-phase peptide synthesis 
  • conduct and enzyme kinetic experiment

 

Competences

  • read and discuss research examples concerning optimization of biologically active peptide drug leads with respect to pharmacological properties including bioavailability and in vitro cytotoxicity
  • apply basic theory of peptide optimization and protein engineering/​expression related to practical development of biopharmaceuticals

 

Lectures: 21
Class sessions: 12
Writing of individual study report (ca. 40 hours during last 3 weeks)
Practical exercises (20 hours in lab)

Selected book chapters:

Peptide Synthesis and Applications, K. J. Jensen, A. P. Tofteng, S. L. Pedersen (Eds), Springer Protocols, Humana Press, 2013.

 

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, nucleic acids and analogues thereof.

All teaching materials besides the textbook will be available via the course homepage or as handout material.

Basic knowledge in organic and bioorganic chemistry and molecular biology is a prerequisite.

Written

Throughout the duration of the course period, students will be given the opportunity to answer multiple choice questions online, to which the answers are provided subsequently. This will provide them with an idea of their level of understanding of the taught curriculum.  

ECTS
2,5 ECTS
Type of assessment
Course participation
Written assignment
Type of assessment details
Course certificate: The students work in groups of 3-5 persons preparing a joint lab journal and report on the performed experiments including answering of the associated questions.
Aid
All aids allowed

The lab teachers may be approached for guidance in answering the associated questions.

Marking scale
passed/not passed
Censorship form
No external censorship
Criteria for exam assessment

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

Knowledge:

  • show that the basic concepts have been understood through answering  the associated questions.
  • show that the basic concepts have been understood.
  • a theoretical background to understand synthesis descriptions of simple chemical reactions involving peptides relevant as biopharmaceuticals.

 

Skills:

  • carry out the laboratory work to satisfaction.
  • perform experiments with acceptable results and described in a scientific way, so that the synthesis and analysis excercises may be repeated.
  • performing simple syntheses and analysis of peptides.

 

Competences:

  • write a report in a scientific language about how the experimental work was performed.
ECTS
5 ECTS
Type of assessment
Written assignment
Type of assessment details
Individual written assignment (essay) in the format of a scientific minireview (size: min 15.000 and 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 directors. The essay must relate to a substantial content of chemistry as well as a biology/​​biopharmaceutical aspect. The student will have 3 weeks to prepare this.
Aid
All aids allowed
Marking scale
7-point grading scale
Censorship form
No external censorship
Criteria for exam assessment

To achieve the grade 12 the student must be able to:

Knowledge

  • comprehend the steps involved in biopharmaceutical drug discovery
  • understand aspects of chemical peptide synthesis relevant for biopharmaceutical drug discovery
  • understand post-translational peptide/protein modifications
  • understand methods used in chemical protein modification
  • understand the concept of unnatural mutagenesis
  • appreciate the potential of novel types of biopharmaceuticals based on nucleic acids (and analogs thereof) in sufficient detail to follow future scientific developments in this field

 

Skills

  • devise chemical synthesis of relevant peptides and modification of protein drugs 
  • search and read relevant literature and use this knowledge in biopharmaceutical research projects.
  • discuss and illustrate how a specific type of biopharmaceuticals may be discovered via synthesis/expression of leads that undergo optimization using appropriate methodologies.

 

Competences

  • read and discuss research examples concerning optimization of biologically active peptide drug leads with respect to pharmacological properties including bioavailability and in vitro cytotoxicity
  • apply basic theory of peptide optimization and protein engineering/​​expression related to practical development of biopharmaceuticals

Single subject courses (day)

  • Category
  • Hours
  • Lectures
  • 21
  • Class Instruction
  • 8
  • Preparation
  • 88
  • Theory exercises
  • 4
  • Laboratory
  • 20
  • Project work
  • 40
  • Exam
  • 25
  • English
  • 206

Kursusinformation

Language
English
Course number
SMPS20001U
ECTS
See exam description
Programme level
Full Degree Master
Duration

1 block

Placement
Block 1
Schedulegroup
C
Capacity
45 students (25 seats reserved students of MSc Programme in Medicinal Chemistry).
Studyboard
Study Board of Pharmaceutical Sciences
Contracting department
  • Department of Drug Design and Pharmacology
  • Department of Chemistry
Contracting faculty
  • Faculty of Health and Medical Sciences
Course Coordinators
  • Kristian Strømgaard   (19-6d746b75766b637030757674716f69636374664275777066306d7730666d)
  • Christian Adam Olsen   (3-6765734477797268326f7932686f)
Study secretary: If you need to contact the study secretary, please the Student Affairs Department contact information (list in Danish only): Afdeling for Uddannelse og Studerende (AUS) – Københavns Universitet (ku.dk)
Teacher

Kristian Strømgaard
Christian A. Olsen
Knud J. Jensen

Saved on the 31-03-2022

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