Chemistry and physical-chemistry of peptide and protein assemblies

Duration

25h Th

Number of credits

Lecturer

Jean-Christophe Monbaliu, Loïc Quinton

Coordinator

Jean-Christophe Monbaliu

Language(s) of instruction

French language

Organisation and examination

Teaching in the first semester, review in January

Schedule

Schedule online

Units courses prerequisite and corequisite

Prerequisite or corequisite units are presented within each program

Learning unit contents

Chemistry and Physico-chemistry of Peptide and Protein Architectures is a series of lectures dedicated to modern concepts in the chemistry and physico-chemistry of peptides and proteins. Peptide- and protein-based therapeutics represent a rapidly expanding field. Currently, more than 70 peptide-based drugs are approved worldwide, with over 140 in clinical trials and more than 500 derivatives in preclinical development. Peptide-based drugs accounted for roughly 10% of all new drugs approved in the US in 2016. Since then, the global peptide therapeutics market has surged, growing from US$14.1 billion in 2018 to an estimated US$117.3 billion in 2024. This growth highlights the pressing need for innovative synthetic methods and technologies to enable their production, characterization, and the study of their physico-chemical properties.

Part A - Preparation of peptides and proteins

Part A offers a thorough introduction to the modern concepts and methods for the preparation of peptides and proteins. While peptides can be obtained through extraction from natural sources or recombinant expression techniques, these approaches will not be covered in this course. Instead, the focus is placed entirely on synthetic methodologies, which offer unmatched precision and flexibility for designing and producing peptides of defined structure. The module begins with a review of amino acids, protecting groups, and activation strategies, which form the foundation of peptide synthesis. Solid-phase peptide synthesis (SPPS), a method that revolutionized the field, is presented as the central technique for assembling peptides efficiently and reproducibly. Advanced topics, such as the design of isopeptides, are introduced to highlight how chemical modifications expand structural diversity. Native chemical ligation and related coupling methods are then discussed as powerful tools for the synthesis of larger and more complex peptide and protein architectures. Throughout Part A, examples from pharmaceutical development are used to illustrate the practical applications of these synthetic strategies.

• Chapter 1: Amino acids, protecting groups, and activation methods
• Chapter 2: Solid-phase peptide synthesis
• Chapter 3: (O)- and (S)-acyl isopeptides
• Chapter 4: Native chemical ligation and advanced methods

• Chapter 1: General approaches for peptide identification and sequencing
• Chapter 2: Theory of fragmentation of protonated peptides by mass spectrometry
• Chapter 3: Impact of post-translational modifications on fragmentation spectra
• Chapter 4: Case studies: mambaquaretin. From the discovery of a snake peptide toxin to its exploitation as a drug candidate

Learning outcomes of the learning unit

At the end of this course, the student will be able to:

• Mobilize the fundamental principles of peptide and protein chemistry (amino acids, protecting groups, activation strategies, solid-phase synthesis).
• Apply advanced synthetic methodologies such as isopeptide design, native chemical ligation, and related coupling techniques for the preparation of complex peptide architectures.
• Critically analyze the advantages and limitations of chemical synthesis compared to extraction or recombinant methods for producing peptides and proteins.
• Understand and apply analytical strategies for peptide sequencing and structural elucidation with mass spectrometry.
• Evaluate experimental constraints related to peptide characterization (limited sample amounts, sensitivity, and specificity of methods).
• Interpret complex case studies involving bioactive peptides from natural sources, particularly animal venom toxins with extensive post-translational modifications.
• Integrate chemical, analytical, and structural knowledge to appreciate the challenges and opportunities of peptide and protein therapeutics in modern science.

Prerequisite knowledge and skills

Fundamental concepts of organic chemistry, physical chemistry and structural chemistry (bachelor degree)

Planned learning activities and teaching methods

Exercises
A wide variety of examples and exercises are integrated throughout both Part A and Part B of the course to illustrate and reinforce the theoretical concepts. These activities are designed to encourage problem-solving thinking and to illustrate theory with practical applications.

The exam questions from previous years are also made available (on MyULiège) for preparation purposes.

 

Laboratory practice
Part B includes a laboratory component. Students will receive training on the use of a mass spectrometer and will each be provided with a purified peptide sample. They will be encouraged to design and conduct their own experiment in order to collect and interpret as much structural and analytical information as possible about this unknown peptide.

For safety reasons, access to the laboratory is permitted only to students wearing a laboratory coat (made of non-flammable fabric) and a pair of safety goggles. The lab coat and goggles must be worn at all times. Specific safety instructions will be reviewed prior to the laboratory activity.

Mode of delivery (face to face, distance learning, hybrid learning)

Delivery of material in a lecture format, face-to-face. Possibility of e-learning (online additional references and resources).

Course materials and recommended or required readings

Platform(s) used for course materials:
- MyULiège

Other site(s) used for course materials
- DOX (https://dox.uliege.be/index.php/s/JGn7GXil2vy3L8i)


Further information:

Platforms used for course materials:

• MyULiège
  
  

• DOX (https://dox.uliege.be/index.php/s/JGn7GXil2vy3L8i)
  
  

Exam(s) in session

Any session

- In-person

written exam ( open-ended questions )


Further information:

Exam(s) in session

All sessions combined

• In person
  Written evaluation (open-ended questions) 

Work placement(s)

Nihil

Organisational remarks and main changes to the course

Chemistry and Physico-chemistry of Peptide and Protein Architectures is offered every other year, only during odd academic years (e.g., 2025-2026, 2027-2028, 2029-2030, etc.), in order to ensure optimal supervision.

Contacts

Jean-Christophe M. Monbaliu
tel 04 366 35 10; email jc.monbaliu@uliege.be  
Loïc Quinton
tel 04 366 36 79; email Loic.Quinton@uliege.be    

Association of one or more MOOCs

Items online