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Chemical Space Inspired Building Blocks and Peptides for Medicinal Chemistry

English title Chemical Space Inspired Building Blocks and Peptides for Medicinal Chemistry
Applicant Reymond Jean-Louis
Number 207976
Funding scheme Project funding
Research institution Departement für Chemie, Biochemie und Pharmazie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Organic Chemistry
Start/End 01.04.2022 - 31.03.2026
Approved amount 1'250'015.00
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Keywords (10)

transfection reagents; computer-aided synthesis planning; antimicrobial peptides; small molecule drugs; dendrimers; protein aggregation ; machine learning; peptides; cheminformatics; chemical space

Lay Summary (French)

Lead
Exploration algorithmique et expérimentale de l'espace chimique à la recherche de nouveaux médicaments
Lay summary

La diversité chimique des principes actifs utilisables comme médicaments est extrêmement vaste. Notre but est d’inventer des méthodes informatiques pour explorer cet espace chimique. Nous programmons des algorithmes utilisant entre autres l'intelligence artificielle qui sont capables d’énumérer des molécules virtuelles encore inconnues, et de prédire leur activité biologique. Pour tester la validité de nos algorithmes, nous synthétisons ces nouvelles molécules et testons leurs propriétés en laboratoire.  Cette approche pourrait transformer la découverte de médicaments en révélant des dimensions inattendues de l’espace chimique ainsi que de nouvelles familles de molécules. Nous nous intéressons en particulier aux petites molécules organiques avec un projet sur les alcaloïdes synthétiques, ainsi qu’aux peptides thérapeutiques dans le domaine des antibiotiques, des réactifs de transfection pour vaccins à ARN messager, et des inhibiteurs d’agrégation pour lutter contre les maladies neurodégénératives et le cancer.

Direct link to Lay Summary Last update: 30.03.2022

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
205330 A nitrogen cooled NMR cryoprobe and a new console for the measurement of low concentrated samples 01.01.2022 R'EQUIP
185544 NCCR TransCure: From transport physiology to identification of therapeutic targets (phase III) 01.11.2018 National Centres of Competence in Research (NCCRs)
165997 Exploiting and Extending GDB for Drug Discovery 01.05.2016 Project funding
178998 Chemical Space Design of Small Molecules and Peptides 01.04.2018 Project funding
159941 A Chemical Space Approach to Bioactive Peptides 01.04.2015 Project funding
196862 Structural and mechanistic investigations of membrane-integral enzymes involved in eukaryotic protein N-glycosylation pathway 01.01.2021 Project funding

Abstract

The chemical space of all possible molecules of interest for medicinal chemistry is extremely large and difficult to grasp. Our goal is to develop computationally driven workflows connecting the theoretical concept of chemical space to actual computations with large databases of molecules, design, synthesis and activity testing in the laboratory. Such workflows can have a transformative effect on drug discovery by uncovering new dimensions and compound classes. We combine computational and experimental approaches in the areas of small molecules and peptides. The first part on small molecules aims to identify and synthesize new building blocks for medicinal chemistry from the chemical space databases GDB originally developed in our group, which enumerate all possible molecules up to a given size, with focus on GDB20 and on polycyclic diamine drug cores as synthetic targets The second part on peptides addresses further developments of our chemical space guided approach to peptide design, with specific projects on machine-learning guided design of antimicrobial peptides, on stereorandomization for antimicrobials and for protein aggregation inhibition, and on mRNA transfection reagents towards vaccine development.
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