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Research projects conducted in Department of Bioorganic Chemistry:

De novo design of cavity-incorporating mini-proteins and their application in catalysis

This proposal concerns de novo design of mini-proteins incorporating cavities and their use for construction of enzyme-like catalysts. Challenging cavity-containing mini-proteins will be constructed using secondary structures incorporating conformationally constrained beta-amino acid residues. Interactions between secondary structures will be maintained by hydrophobic interactions in some cases supported by disulfide bridges. Subsequently, the application of developed cavity-containing mini-proteins for construction of enzyme-like catalysts will be explored. Iterative optimization of catalytic activity by computer-aided modifications of both substrate binding cleft and distant residues will provide access to proficient catalysts. We will focus on three groups of reactions: (a) aldol condensation and related reactions mediated by enamine intermediate; (b) conjugate additions and cycloadditions proceeding via iminium intermediate. Read more...


Hairpin.jpg Utilization of π-cation stabilized β-hairpin for construction of hybrid tertiary structures

In this project we plan to obtain highly stable hybrid tertiary folds by combining two stable secondary structures: foldameric helix containing cyclic β-amino acids and π-cation-stabilized β-hairpin. The π-cation stabilization, while present in native proteins, was not yet utilized in the design of miniproteins. Read more...

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...

URE-1.jpg 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...

Development of modification method for organic foldamers on the resin, used in the design of molecular probes, and assessment of its usefulness in the synthesis of the library of molecular probes

The developed approach will accelerate the synthesis of extensive and diverse foldamer libraries, and thus allow more efficient testing of their interaction with selected molecular surfaces. This will allow faster identification of ligands able to interact effectively with selected macromolecules. Read more...

Aminophosphonates bearing fluorine atoms as inhibitors odf aminopeptideses and their potential application for determination of enzyme-inhibitor interactions

This project considers construction of inhibitors containing both phosphorus and fluorine atoms in their structure, atoms which enable to detect and follow by NMR small changes around the inhibitor and thus to deduce the exact structure of the enzyme upon its binding. Basing on the experience of authors of the project such inhibitors will be constructed and synthesized and their utility will be evaluated. The results of the project should not only help in better understanding of the enzyme architecture, form a basis for the design of novel drugs but also to obtain of inhibitors able to act towards aminopeptidases, which are considered as targets for anticancer agents. Read more...

Hydrogen bond donors in non-classical asymmteric catalysis

The project is focused on the application of more sustainable and thus non-classical methods in asymmetric catalysis. Hydrogen bond donors which structure will be tuned for specific task are the main group of catalysts. Among the activation methods, ball-milling, microwave-assisted processes and the application of hydrophobic amplification will be particularly developed. 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

The main goal of the project involves rational design of peptide foldamers to be exploited as building blocks for the controlled self-assembly of nanomaterials. Foldamers are oligomers that exhibit a define tendency to folding to stable 3D structure in solution and possess enormous potential among synthetic self-organizing systems to mimic the regular structural behavior of biomolecules. Virtually unexplored is a subject of self-organization of complex α,β-peptides. That is why, there will be carried out studies in order to increase knowledge regarding design, synthesis and aggregation of peptides containing both α- and β-residues, which can be potentially applied in the synthesis of bionanomaterials with a vast range of applications. Read more...

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...