Rafał Latajka

• Professor
• Professor (Full) at Wrocław University of Science and Technology

Peptides conjugated with organic molecules can be useful tools for the development of novel bioactive compounds. The lysine side‐chain is an interesting functional group to act as a linker to connect small molecules in peptide conjugates. Herein we present the design and synthesis of four Safirinium derivatives, their facile conjugation to lysine i...

Research on new compounds that can improve the skin's condition is no longer focused exclusively on drugs, but is also adequate for cosmeceuticals – cosmetic products with thoroughly tested and scientifically proven biological activity. One of the most important stimulators of collagen biosynthesis is the so-called Transforming Growth Factor-β (TGF...

Oxytocin (OT) is a neurohypophyseal peptide hormone containing a disulphide-bridged pseudocyclic conformation. The biomedical use of OT peptides is limited amongst others by disadvantageous pharmacokinetic parameters. To increase the stability of OT by replacing the disulphide bridge with the stable and more rigid [1,2,3]triazol-1-yl moiety, we emp...

The publication reviews the results on the tyrosinase inhibition capacity of a short peptide and peptide conjugates with known low molecular weight inhibitors of this enzyme. Tyrosinase is a widespread copper-dependent enzyme capable of catalyzing two reaction pathways for oxidizing monophenols to o-diphenols and o-diphenols to o-quinones. Despite...

The development of skin-care products is recently growing. Cosmetic formulas containing active ingredients with proven efficacy, namely cosmeceuticals, are based on various compounds, including peptides. Different whitening agents featuring anti-tyrosinase activity have been applied in the cosmeceutical field. Despite their availability, their appl...

The interests of the research group working under the supervision of professor Rafał Latajka at the Department of Bioorganic Chemistry at the Wrocław University of Science and Technology are focused on several projects in the field of biological chemistry. Regardless of whether a given project concerns – the synthesis and activity of new enzyme inh...

The involvement of Myelin Basic Protein (MBP) in Multiple Sclerosis (MS) has been widely discussed in the literature. This intrinsically disordered protein has an interesting α-helix motif, which can be considered as a conformational epitope. In this work we investigate the importance of the helical structure in antibody recognition by MBP peptides...

The interests of the research group working under the supervision of professor Rafał Latajka at the Department of Bioorganic Chemistry at the Wrocław University of Science and Technology are focused on several projects in the field of biological chemistry. Regardless of whether a given project concerns – the synthesis and activity of new enzyme inh...

Synthesis of a new group of hybrid phosphonodehydropeptides composed of glycyl-(Z)-dehydrophenylalanine and structurally variable aminophosphonates alongside with investigations of their activity towards cathepsin C are presented. Obtained results suggest that the introduction of (Z)-dehydrophenylalanine residue into the short phosphonopeptide chai...

The development of peptide stapling techniques to stabilise α-helical secondary structure motifs of peptides led to the design of modulators of protein–protein interactions, which had been considered undruggable for a long time. We disclose a novel approach towards peptide stapling utilising macrocyclisation by late-stage Suzuki–Miyaura cross-coupl...

Dobutamine and dopamine have been previously shown to interfere with enzymatic diagnostic tests and different mechanisms responsible for this effect have been postulated. We have studied the oxidation by horseradish peroxidase (HRP) of dopamine, dobutamine and its analog with the phenol group blocked by methylation. Oxidation of dobutamine was much...

Collagen fibres degradation is a complex process involving a variety of enzymes. Fibrillar collagens, namely type I, II, and III, are the most widely spread collagens in human body, e.g., they are responsible for tissue fibrillar structure and skin elasticity. Nevertheless, the hyperactivity of fibrotic process and collagen accumulation results wit...

Peptidomimetics play a fundamental role in drug design due to their preferential properties regarding natural peptides. In particular, compounds possessing nitrogen-containing heterocycles have been intensively studied in recent years. The triazolyl moiety incorporation decreases the molecule susceptibility to enzymatic degradation, reduction, hydr...

Phosphinate pseudopeptide are analogs of peptides containing phosphinate moiety in a place of the amide bond. Due to this, the organophosphorus fragment resembles the tetrahedral transition state of the amide bond hydrolysis. Additionally, it is also capable of coordinating metal ions, for example, zinc or magnesium ions. These two properties of ph...

Cosmeceutical field, which merges cosmetics and pharmaceuticals , is nowadays a highly investigated research area, because a scientific demonstration of the claimed bioactivity of new cosmeceutical ingredients is increasingly requested. In fact, an aspect differentiating traditional cosmetics from cosmeceuticals is the identification and characteri...

A set of 12 monosubstituted acetophenone thiosemicarbazone derivatives (TSCs) were synthesized and their inhibitory properties toward tyrosinase activity were tested. Moreover, their ability to inhibit melanogenesis in the B16F10 murine melanoma cell line was studied. In order to investigate the nature of interactions between the enzyme and the inh...

Among the many aspects that contribute to the wellness of each individual, healthy and younger-looking skin play a relevant role, as clearly shown by the important growth of the skin-care products market observed in recent years. In this scenario, the field of cosmeceuticals appears particularly promising, being based on cosmetic products containin...

This review discusses the coordination ability of peptides containing β-amino acid residues incorporated into their sequence. Special attention is given to the importance of βAla residue and metal binding affinity of transition metal ions, especially Cu2+ ion. The coordination process occurs analogously to peptides composed of α-amino acids. The co...

Mimo że dehydropeptydy są znane jako peptydomimetyki o specyficznych preferencjach konformacyjnych, już od kilkudziesięciu lat nadal są interesującym obiektem badawczym. Zarówno mnogość struktur czy sekwencji, jak i możliwość kontrolowania warunków (takich jak temperatura czy rozpuszczalnik) czynią z reszt dehydroaninkowasowych bardzo efektywny czy...

Antifreeze glycoproteins are a class of biological agents which enable living at temperatures below the freezing point of the body fluids. Antifreeze glycopeptides usually consist of repeating tripeptide unit (-Ala-Ala-Thr*-), glycosylated at the threonine side chain. However, on the microscopic level, the mechanism of action of these compounds rem...

The group of 10 phosphonic and phosphinic acid derivatives containing pyridine moiety were synthesized and its inhibitory activity toward mushroom tyrosinase were investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. All the compounds (1‐10) demonstrated the inhibitory effect with the inhibitio...

Peptidotriazolamers are hybrid foldamers with features of peptides and triazolamers, containing alternation of amide bonds and 1,4-disubstituted 1H-1,2,3-triazoles with conservation of the amino acid side chains. We report on the synthesis of a new class of peptidomimetics, containing 1,4-disubstituted 1H-1,2,3-triazoles in alternation with amide b...

Tyrosinase plays an essential role in melanogenesis. Excess production of melanin can be a reason of hyperpigmentation skin disorders in mammals and enzymatic browning in plant-derived foods. Catalyzing the rate-limiting step of melanin synthesis, tyrosinase has become the most studied target for melanogenesis inhibition. For over the past ten year...

The group of 19 thiosemicarbazones (TSCs) were synthesized and its inhibitory activity toward mushroom tyrosinase and ability to inhibition of melanogenesis in B16 cells were investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. The obtained results allowed to make the structure-activity relati...

Two novel, sterically hindered platinum(II) complexes Pt(Oro)(NH3)(2-pic), 1, and Pt(5-FOro)(NH3)(2-pic), 2, were synthesized by connecting the cis-[Pt(NH3)(2-picoline)]²⁺ fragment of picoplatin (new anticancer agent, being currently under clinical trials) with the chelating orotate or 5-fluoroorotate bioactive ligands. The complexes were character...

Peptidotriazolamers are hybrid foldamers combining features of peptides and triazolamers - repetitive peptidomimetic structures with triazoles replacing peptide bonds. We report on the synthesis of a new class of peptidomimetics, containing 1,5-disubstituted 1,2,3-triazoles in an alternating fashion with amide bonds and the analysis of their confor...

Peptidomimetics are molecules of particular interest in the context of drug design and development. They are proteolytically and metabolically more stable than their natural peptide counterparts, but still offer high specificity towards their biological targets. In recent years, 1,4- and 1,5-substituted 1,2,3-triazole-based peptidomimetics have eme...

Addition of thiols to double bond of glycyl-dehydroalanine and phenyl-dehydroalanine esters provided micromolar inhibitors of cathepsin C. The structure-activity studies indicated that dipeptides containing N-terminal phenylalanine exhibit higher affinity towards the enzyme. A series of C-terminal S-substituted cysteines are responsible for varying...

Antifreeze glycopeptides (AFGPs) are a class of biological antifreeze agents found predominantly in Arctic and Antarctic species of fish. They possess the ability to regulate ice nucleation and ice crystal growth, thus creating viable life conditions at temperatures below the freezing point of body fluids. AFGPs usually consist of 4–55 repetitions...

Hydrophobic zinc (II) phthalocyanine-type derivatives, solubilized in polymeric micelles (PMs), provide a befitting group of so called nanophotosensitizers, suitable for a variety of photodynamic therapy (PDT) protocols. The factors that influence the success of such products in PDT are the location of the active cargo in the PMs and the nanocarrie...

The cysteine protease family members play important roles in various pivotal cellular processes. The difficulty in the analysis of the effects of cysteine protease aberrationsin cancer comes as a result of the fact that they take part in complex proteolytic pathways. Nevertheless, there is a vast amount of data regarding the involvement of distinct...

Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic s...

Structural studies of pentapeptides containing an achiral block, built from two dehydroamino acid residues (Δ(Z)Phe and ΔAla) and two glycines, as well as one chiral L-Val residue were performed using NMR spectroscopy. The key role of the L-Val residue in the generation of the secondary structure of peptides is discussed. The obtained results sugge...

Effective peptidomimetics should posses structural rigidity and appropriate interaction pattern leading to potential spatial and electronic matching to the target receptor site. Rational design of such small bioactive molecules could push chemical synthesis and molecular modeling toward faster progress in medicinal chemistry. Conformational propert...

Structural investigations of dehydropeptides containing (Z)-dehydrophenylalanine in solvents characterized by different polarity are discussed. The conformational analysis are based on spectroscopic methods (NMR, CD), molecular modeling techniques and in case of the tripeptide, ab initio methods. The results of temperature experiment indicate, that...

Conformations of two pairs of dehydropeptides with the opposite configuration of the ΔPhe residue, Boc‐Gly‐Δ Z Phe‐Gly‐Phe‐OMe ( Z‐ OMe ), Boc‐Gly‐Δ E Phe‐Gly‐Phe‐OMe ( E‐ OMe ), Boc‐Gly‐Δ Z Phe‐Gly‐Phe‐p‐NA ( Z‐p‐ NA ), and Boc‐Gly‐Δ E Phe‐Gly‐Phe‐p‐NA ( E‐p‐ NA ) were compared on the basis of CD and NMR studies in MeOH, trifluoroethanol (TFE), Me...

The reactions of adenosine with malonaldehyde and glyoxal, and with malonaldehyde and methylglyoxal resulted in the formation of one malonaldehyde-glyoxal and one malonaldehyde-methylglyoxal conjugate adduct, respectively. These adducts were isolated and purified by reversed-phase liquid chromatography, and structurally characterized by UV, (1)H- a...

Conformational preferences of a group of hexapeptides containing two dehydroamino acid residues in Positions 2 and 5 in peptide chain were investigated by means of spectroscopic methods (NMR and CD) and theoretical calculations. In the case of dimethylsulfoxide (DMSO) solution, only peptide with free N-termini adopted rigid 310-helical conformation...

Synthesis, structural and biological studies of pentapeptides containing two DeltaPhe residues (Z and E isomers) in position 2 and 4 in peptide chain were performed. All the investigated peptides adopted bent conformation and majority of them could exist as two different conformers in solution. Only pentapeptides, containing free N-termini appeared...

Biotransformation of diethyl of 2-oxo-2-phenylethylphosphonate using different fungal cells as biocatalysts yielded optically active O-phosphorylated derivative of 2-hydroxy-2-phenylethylphosphonate of satisfactory enantiomeric excess up to 99%.

Conformational investigations of a group of bis(α-aminoalkyl)phosphinic acids were performed by use of NMR spectroscopy and theoretical calculations. In the case of one of the studied compounds, substituted with aminobenzyl and amino(p-chlorobenzyl) moieties, a pH-dependent equilibrium between conformers, stabilized by intermolecular hydrogen bonds...

Two series of dehydropeptides of the general formulae Boc-Gly-X-Phe-p-NA, Boc-Gly-Gly-X-Phe-p-NA, Gly-X-Gly-Phe-p-NA·TFA, and Boc-Gly-X-Gly-Phe-p-NA, with X = ΔZPhe and ΔAla, were studied with NMR in DMSO and CDCl3-DMSO, and with CD in MeOH, MeCN, and TFE. The NMR spectra measured in DMSO suggest that peptides with the ΔPhe residue next to Phe are...

Recently, bisaminophosphonates found applications as therapeutic agents for curing bone disorders. When trying to relate the structures of substituted piperid-1-ylmethylenebisphosphonic with their biological properties, non-typical findings that in 31P NMR spectra of 2-methyl-piperid-1-ylmethylenebisphosphonic and 2-ethyl-piperid-1-ylmethylenebisph...

Alkyl monoesters of N-substituted aminophosphonic acids have been prepared by heating of the corresponding dialkyl aminophosphonates oxalate salts in water. The formed monoesters were separated as crystalline solids from the aqueous reaction mixture.

Tetrapeptide p-nitroanilides containing (E)-dehydrophenylalanine were synthesized and evaluated as inhibitors and substrates of cathepsin C. Peptides containing a free, unblocked amino group appeared to be quite good substrates of the enzyme, whereas fully protected peptides acted as very weak inhibitors. Structural studies by means of NMR and CD,...

Starting from (+)-3-carene I several chiral fragrant compounds with the bicyclo[3.1.0]hexane system 4-6 and 10-20 were synthesized. These compounds are structural analogues of naturally occurring fragrant compounds, such as ionones and damascones, and possess either an endo- or an exo-cyclic double bond in the bicyclo[3.1.0]hexane moiety. The absol...

The structure of 2-aminoindane-2-phosphonic acid (AIP) was studied using X-ray crystallography, NMR spectroscopy, molecular modelling, IR spectroscopy, and potentiometric titration. In the solid state, a thermodynamically stable conformer of AIP is one in which the phosphonic group occupies the equatorial position and the amino group the axial posi...

The formation constants of equimolar and bis-chelate copper(II) and zinc(II) complexes with three aliphatic and four aromatic-substituted β-aminophosphonates have been determined in water solution by potentiometric studies. Spectroscopic parameters clearly indicate involvement of {NH3, PO32−} in both metal ions coordination. The comparison of the s...

The highly stereoselective synthesis of (1S,2S)-2-amino-1-hydroxyalkylphosphonic acids was achieved by addition of dimethyl phosphite to N-protected aminoaldehydes. Relative configuration and solution conformations of (1S,2S)-2-amino-1-hydroxy-alkylphosphonic acids (in D2O) and their dimethyl esters (in CDCl3 and CD3OD) were established by means of...

Acid-base properties and metal-binding abilities of tris(2-carboxyethyl)phosphine (TCEP), a newly introduced thiol group protectant, were studied in solution, using potentiometry, (1)H and (31)P NMR, and UV-vis spectroscopy, and also in the solid state by X-ray diffraction. Stability constants of complexes of the P-oxide of TCEP (TCEPO) were establ...

Potentiometric, 1H, 31P NMR spectroscopic and X-ray studies were carried out to investigate the complex formation of Al(III) with iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), their mixed carboxylic–phosphonic and purely phosphonic derivatives. The stability constants of the complexes formed were determined at 25 °C and at 0.2 mol dm−3 ion...

Depending on the pH of the medium or temperature, one or two phosphorus signals were observed on 31 P NMR spectra of 4-aminopiperid-4-yl phosphonic acids, indicating slow conformational ring interconversion. The experimental data have been correlated with theoretical results obtained by calculations using semiempirical methods (PM3), DFT, and the P...

Conformations of 2-amino-1-hydroxy-2-aryl ethylphosphonic acids (in D2O) and their diethyl esters (in CDCl3 and CD3OD) were determined by means of NMR on the basis of dependence between observed values of coupling constants (3JPC, 3JHH and 3JPH) and corresponding dihedral angles. In case of diethyl esters we observed that the conformation was stabi...

Treatment of chromone-2, coumarin-4 and pyrone-2 derivatives of N-benzylaminomethylphosphonic acid with strong mineral acids leads to formation of the corresponding heterocyclic amines and phosphoric acid. Kinetic studies of this cleavage reaction demonstrate that protonation has a remarkable influence on a cleavage of C-P bonds. In aq. H2SO4, clea...

Three dehydrotetrapeptides of rationally varying structure were prepared and tested as affectors of cathepsin C. These compounds appeared to be substrates of the enzyme, being equipotent with their classical counterparts. Thus, replacement of amino acid in a short peptide by corresponding dehydroamino acid does not prevent cathepsin C in recognizin...

In 31P NMR spectra of derivatives of 1-amino- and 1-hydroxypiperid-4-ylphosphonic acids, fully reversible conformational equilibria in aqueous and methanolic solutions were observed. Depending on the pH of the medium and temperature, one or two phosphorus signals were observed indicating slow conformational ring interconversion under specific condi...

The conformations of diethyl 2-hydroxypropylphosphonate in CDCl3 were studied by means of NMR spectroscopy. This compound forms species in which intermolecular hydrogen bonding prevails in concentrated solutions whereas intramolecular bonds are predominant in dilute solutions. Usually both types of species exist in dynamic equilibrium and the forma...

Studies of the acid-catalyzed cleavage of 2-pyridyl and 4-pyridyl(amino)methylphosphonic acids demonstrate that protonation has a profound effect on the cleavage of C-P bonds. In H2SO4, and other strong mineral acids the cleavage of aminophosphonic acids 1 and 4 exhibits a kinetic depedence on Zucker-Hammett acidity function (ho), with rate law, v...

A combined pH-metric and spectroscopic (UV—Vis, circular dichroism and electron paramagnetic resonance) study of Cu(II) binding to analogues of Asn-Ser-Phe-Arg-Tyr-NH2 systematically substituted with Ala residues revealed the presence of indirect, additive conformational effects resulting in a very high stability enhancement for 4N complexes. The m...