How to enhance the activity of peptides in the fight against viruses and microbes

The ALANINE project, winner of the 2023 CY Initiative call for proposals, is based on the convergence of two strong and complementary areas of expertise. Nadège Lubin-Germain, professor in the Chemistry Department at CY Cergy Paris University, works in the BioCIS laboratory, which is affiliated to CY Cergy Paris University, CNRS and Paris-Saclay University. As a molecular chemist, she specializes in synthesizing molecules with specific properties.

Working with Abdelghani Oukhaled was an obvious choice for this project.  He is a teacher-researcher in the LAMBE laboratory, a CNRS unit also associated with Paris-Saclay and CYU. Professor Oukhaled is developing a technique that enables the manipulation of molecules one by one, thus helping us to understand their characteristics. Few teams in France or elsewhere in the world are working in this field. 

Complementarity at the heart of the project 

"In the group, we've been interested for a long time in delivering bioactive molecules in a targeted, active way. It's not a matter of free diffusion, but of targeted delivery to a specific location, and with greater ease. In concrete terms, this means that the molecule doesn't go anywhere on an organ, and above all, that once it's in the organ, it easily enters the cell", notes Nadège Lubin-Germain. This requires several molecular tools, which are in fact small portions of proteins or macromolecules. Some of these biological macromolecules are called peptides.   

As part of this project, Prof. Lubin-Germain is interested in how these peptides interact with cell membranes. For example, they facilitate the entry of a drug into the cell. The aim is to study what these peptides are, how to modify them to make them more active on the membrane, and how they penetrate the cell. This is precisely one of the areas of expertise of Professor Abdelghani Oukhaled, who has developed a technique that enables him to understand the characteristics of these molecules: “In my research, I look at how external molecules can enter the cell through specific proteins known as pores. The aim is to help Professor Lubin-Germain study these peptides".   

How can peptides be made more active?   

This CY Initiative call for proposals winning project has two main objectives.  The first is fundamental: involving the understanding of peptides, which are currently under-studied. In particular, this will involve studying their behavior in contact with cellular pores, a subject studied by Prof. Abdelghani Oukhaled.   

The second objective is to add value to the peptides themselves. “Once we've synthesized and studied the peptides we've created, we're going to try to identify peptides that are highly active on membranes, so that we can use and exploit them in drug delivery to make them more effective and targeted,” notes Nadège Lubin-Germain.  

To achieve this, the two researchers will start with known peptides, modifying them to make them more active on membranes, and even potentially enabling them to destroy these membranes. This could lead to the development of bio-active compounds that could act against viruses or bacteria. All the peptides synthesized will also be studied for antiviral activities in collaboration with a group of researchers in Poland and with Prof. Damien Seyer, biologist at CY Cergy Paris University (Errmece).   

The first peptides synthesized and characterized   

The project was launched with the help of a PhD student who joined the team in September 2023 for a 3-year period.  "At this stage, we have already identified the peptides that will be synthesized and then characterized at BioCIS. Our doctoral student, Camille Dejoux, has already begun synthesizing certain peptides, so in my laboratory we're trying to understand how they work,” notes Abdelghani Oukhaled.   

Nadège Lubin-Germain adds, “It's not a question of synthesizing everything and then analyzing it. We go one step at a time, which allows our PhD student to follow and work on both stages: synthesizing and characterizing. This enables her to understand and master the entire project."  

However, the biological study of antiviral and antibacterial potential will only be carried out once all the peptides have been synthesized. Indeed, to ensure the consistency of the tests and thus obtain reliable results, it is essential to test all the peptides under strictly identical conditions.   

Overall, the aim is to synthesize around thirty peptides. "It's a real challenge to make these peptides more active, and even more challenging to make them antiviral and antimicrobial peptides. We'll have to synthesize a lot of them to understand what needs to be done to make them active. "comments Nadège Lubin-Germain.  

The CY Initiative call for projects enabled three laboratories to work together. “It enabled us to meet and structure ourselves to carry out multidisciplinary research,” notes Abdelghani Oukhaled. The next major steps are to share this novel approach and the initial results at professional conferences, and to obtain European funding for the continuation of the project.