Research projects conducted in Department of Bioorganic Chemistry:
| Peptide foldamer-based inhibitors of human ACE2 – SARS-CoV-2 S protein interaction
The main goal of the project is to develop new compounds from the group of peptide foldamers that would be able to inhibit the interaction of human ACE2 and SARS-Cov-2 virus S protein. Peptides containing rigid fragments will be used to construct planned inhibitors of protein-protein interactions. This approach will allow to effectively optimize the required biological activity by placing appropriate functional groups on the surface of the foldamer and simultaneously controlling its three-dimensional structure. Two groups of foldamer structures are planned as scaffolds for molecules: helix and mini-proteins. The compounds will be designed using computer methods and obtained and analyzed using modern methods of peptide chemistry. The whole process will be repeated iteratively to obtain molecules with the desired inhibitory activity. Read more...
| Dual-action mode inhibitors of urease and their anti-virulent activity against Helicobacter pylori and Cryptococcus neoformans
We wish to envisage within the current project a concept of urease inhibition by dually acting compounds, constructed to combine the reactivity toward the SH of the cysteine with potent nickel-binding properties. An extensive set of new structures is planned to be obtained, their affinity to model and pathogenic ureases measured and the mode of action confirmed. Importantly, selected virulent bacterial and fungal strains will be targeted in whole-cell experiments. The results are expected to bring high-affinity compounds that will be validated as potent and selective agents targeted against Helicobacter infections and cryptococcosis. Read more...
| De novo designed, structurally extended peptide foldamers and their use for construction of PD-1/PD-L1 interaction inhibitors
The main goals of this project include the development of computer-aided methodology for de novo construction of structurally extended peptide foldamers of chosen geometry, and the application of created structures as scaffolds for building effective inhibitors of chosen protein-protein interactions, namely PD-1/PD-L1, that could be applied for cancer immunotherapy. Read more...
|Dehydropeptides as substrates in synthesis of building blocks useful in obtaining artzymes
Catalysts, which structure bases on short peptides (proteins of reduced size) are broadly termed “artzymes”. They are constructed in such a manner that part of the peptide guarantees specific architecture for the catalyst, while second part is responsible for enzyme-like activity. This approach has been successful in many cases. Chemistry knows many reactions, which are not catalyzed by enzymes and for which specific chemical catalysts, have been found. This project is focused on synthesis of such catalysts, which might be called hybrid ones. They are composed of pepetidyl fragment responsible for proper three-dimensional structure of the catalyst and the fragment ensuring chemical catalysis. Thus, the goal of the project is to obtain mini-proteins able to catalyse any chemical reactions. Read more...
|Nanostructures based on peptide foldamers|
| Foldameric miniproteins - structure and catalytic function
This research proposal is related to studies on foldamers that will be able to form protein-like three-dimensional structures. Basing on known alpha-peptidic mini-protein templates and the toolbox of previously studied foldameric secondary structures, we plan to present a rational strategy for the construction of extended protein-like foldameric structures (foldameric mini-proteins). Subsequently, we plan to use the discovered scaffolds for the development of enzyme mimetics. The grafting of the chosen enzyme active sites on elaborated molecular architectures will lead to catalytically active molecules. Four enzyme classes (metallohydrolases, serine hydrolases, aldolases and epoxide hydrolases) are planned to be mimicked. Read more...