Structural and functional biomimetics

Team leader: prof. dr hab. Aleksandra Misicka-Kęsik

Team leader’s e-mail address: misicka@chem.uw.edu.pl

Brief description of the research topic:

In the research group of Peptides, Peptidomimetics, and Foldamers, we focus on the synthesis of peptides and peptide derivatives, including peptidomimetics and oligourea foldamers with a broad spectrum of biological activities and intriguing physicochemical properties.

Cancer and bacterial infections—especially those resistant to antibiotics—continue to pose significant challenges to modern medicine. In our group, we attempt to address these issues by designing peptides and peptidomimetics that act as inhibitors of the VEGF-A165/NRP-1 complex, which may potentially exhibit antiangiogenic properties and can inhibit the formation of new blood vessels during tumor development. Furthermore, the peptides and their derivatives that inhibit the VEGF-A165/NRP-1 complex, when radiolabeled, may be used as vectors for imaging pathological angiogenesis associated with early stages of malignant tumor formation. In the search for new chemotherapeutic agents to combat cancer, we are conducting research on novel peptidomimetics designed to act as intercalators that selectively bind to DNA sequences found, among others, in oncogenes. Upon binding, they induce unstacking and unwinding of the base pairs. To counteract the growing resistance of bacteria to commonly used antibiotics, we are searching for new compounds with various mechanisms of action. We design and synthesize peptides and pseudopeptides that act as inhibitors of the bacterial enzyme HtrA, a member of the serine protease family. By blocking HtrA protease activity, we destabilize critical intracellular bacterial processes. A second group of antibacterial compounds includes amphiphilic helical oligourea foldamers, whose sequences and modes of action resemble those of antimicrobial peptides (AMPs). These compounds damage bacterial cell membranes. So far, we have obtained compounds with high activity, particularly against Gram-positive bacteria, and with strong resistance to digestive enzymes. Using mass spectrometry methods, we investigate the stability of peptides, peptidomimetics, and foldamers in body fluids.

We also use these methods to profile plant metabolites and metabolites in neural tissue homogenates (peptidic, lipidic, and steroidal), as well as to identify metabolic pathways. Additionally, we explore the mechanisms of gas-phase catalytic reactions using this technique. We also study oligourea foldamers from the perspective of supramolecular chemistry. We investigate their self-assembly and ability to interact with cations and anions, as well as the influence of these interactions on self-organization processes. Oligourea foldamers have also proven to be excellent mediators of electron transport. Another area of our research involves the use of computational methods for energy analysis of the degradation of organic components in atmospheric aerosols in the gas phase, and molecular modeling of reaction mechanisms using quantum chemistry techniques.

Peptides and Peptidomimetics

inhibitors of the VEGF-A165/NRP-1 complex
inhibitors of the bacterial enzyme HtrA
DNA intercalators
investigation of enzymatic hydrolysis products and metabolic pathways

Oligourea Foldamers

compounds with antibacterial activity
self-assembly and interaction with cations and anions
electron transport mediators

Computational Techniques

atmospheric aerosols
reaction mechanisms