Research Area

Research conducted in the Laboratory of Peptide Chemistry focuses on the search for the structure-activity relationship of biologically active peptides. These studies include peptide synthesis, purification, evaluation of biological activity and conformation studies.

Pro-protein convertases (PCs)

Pro-protein precursor convertases (PCs) are a family of nine serine proteinases (PC1/3, PC2, PACE4, PC4, PC5/6, PC7, PCSK9, SKI-1) whose activity depends on the concentration of calcium ions. These enzymes are responsible for the posttranslational conversion and activation of a number of precursor proteins into their active forms. PCs are fundamental to the proper functioning of the cell and the regulation of a number of physiological processes occurring in living organisms. The list of substrates activated by proprotein convertases includes numerous hormones, neuropeptides, receptors, enzymes including extracellular matrix metalloproteases, as well as growth factors. The proteolytic activity of pro-protein convertases not only enables the body to function properly, they are also responsible for the initiation and development of many serious pathophysiological conditions. Among other things, their activity leads to the development of cancer, heart disease, Alzheimer's disease, hyperglycemia, and promotes bacterial and viral infections.

Bradykinin (BK)

Bradykinin (BK, Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg), one of the best known kinins, is a 9-peptide involved in the pathogenesis of many diseases, such as allergy, asthma, arthritis, anaphylactic shock, hypertension or acute pancreatitis. The action of kininogenases on kininogens results in the release of kinins: the nonapeptide bradykinin (BK) or the decapeptide calidin (KD, Lys-BK), from which bradykinin is released by limited hydrolysis. Kinins are recognized by two types of receptors. B2R receptors are commonly found in normal tissues, while B1R receptors are expressed on the cell surface as a result of pro-inflammatory factors or under pathological conditions. BK and KD selectively activate B2R receptors, while their metabolites desArg9-BK and desArg10-KD interact only with B1R receptors. The sequence similarity of the two kinin receptors is only 36%. The greatest differences are observed within the extracellular and intracellular loops. Due to the lower concentration of bradykinin in plasma than in tissues, the rapid conversion of KD to BK under the influence of aminopeptidases, and the higher affinity of BK for common B2R receptors, bradykinin is mainly responsible for the biological functions of kinins. In recent years, special attention has been paid to bradykinin analogs with antagonistic effects. Kinin receptor antagonists can be successfully used in the treatment of pain, inflammatory reactions, or cancer.

Neurotensin

Neurotensin is an oligopeptide composed of thirteen amino acid residues. It belongs to the group of neuropeptides. It is detected in the blood, in the cerebrospinal fluid and in the tissues of numerous organs (heart, lung, liver, spleen, pancreas). Neurotensin has a hormonal effect in the small intestine. In the gastrointestinal tract, it is produced in the neuroendocrine cells of the small intestinal mucosa under the influence of the products of fat and protein digestion. Its release enhances pancreatic and intestinal juice secretion, inhibits gastric juice secretion, increases intestinal motility and increases blood flow through the visceral circulation. Neurotensin is also found in the central nervous system, in dopaminergic neurons within the hypothalamus, and in cholinergic ganglionic neurons. One of the most important central tasks of neurotensin is the regulation of neuroendocrine centres. Among other things, the hormone affects the neurons that produce gonadotropin-releasing hormone, somatostatin and corticotropin-releasing factor.

β-Defensin

Defensins are a group of immune peptides, defined as endogenous peptides with high antimicrobial activity. Based on the structure of their precursors, the length of the peptide chain and the location of the disulfide bridges, they are divided into α-, β- and θ-defensins. Their action against viruses, bacteria and fungi is not just down to a direct effect on them. They also have the ability to activate the immune system through signal transduction and regulation of inflammatory pathways. Defensins are widely distributed in the bodies of many vertebrates and invertebrates and even among plants. Only α - and β-defensins have been identified in human organisms. Human β-defensins are polypeptides containing up to forty-some amino acid residues with a characteristic cysteine motif (Cys1-Cys5, Cys2-Cys4, Cys3-Cys6) and a relatively high content of arginine and lysine residues.  Dozens of open reading frames possessing β-defensin-specific motifs have been identified in the human genome. However, only four of these, hBD1-4, are characterised in detail, including a detailed description of their structures (crystallographic data). In addition, the structure of hBD6 in solution (NMR) is described.