Department of Bioorganic Chemistry is one of 15 departments of Faculty of Chemistry, Wrocław University of Technology. It was founded in 1971 by Professor Przemysław Mastalerz in response to introduction of biochemistry and biotechnology curricula at Faculty of Chemistry. Now it is headed by Professor Paweł Kafarski and formed by 6 professors, 10 assistant professors and over 25 PhD students doing research on a border of chemistry and biology.
Recent papers Baker’s yeasts driven synthesis of enantiomers of ethyl 1-hydroxy-1-(3,4-dimethoxyphenyl)methane(P-phenyl)phosphinate - possible organophosphorus CDA’s
Żymańczyk-Duda E, Kozyra K, Brzezińska-Rodak M, Klimek-Ochab M Journal of Molecular Catalysis. B, Enzymatic 2017
, 1DOI: 10.1016/j.molcatb.2017.01.017
Recent papers Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products
Miszczyk, P.; Wieczorek, D.; Gałęzowska, J.; Dziuk, B.; Wietrzyk, J.; Chmielewska, E. Molecules 2017
, 1DOI: 10.3390/molecules22020254 Abstract
The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction—namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid
Recent papers Three-Component Reaction of Benzylamines, Diethyl Phosphite and Triethyl Orthoformate: Dependence of the Reaction Course on the Structural Features of the Substrates and Reaction Conditions
Miszczyk, P.; Turowska-Tyrk, I.; Kafarski, P.; Chmielewska, E. Molecules 2017
, 1DOI: 10.3390/molecules22030450 Abstract
The reaction between benzyl amines, triethyl orthoformate, and diethyl phosphite affords either bisphosphonic or N-benzylaminobenzylphosphonic acid depending on the reaction conditions. The final output of the reaction can be manipulated by the choice of reaction conditions, particularly the molar ratio of substrates.
Recent papers Highly sensitive and adaptable fluorescence-quenched pair discloses the substrate specificity profiles in diverse protease families
Poreba M, Szalek A, Rut W, Kasperkiewicz P, Rutkowska-Wlodarczyk I, Snipas SJ, Itoh Y, Turk D, Turk B, Overall CM, Kaczmarek L, Salvesen GS, Drag M Scientific Reports 2017
, 1DOI: 10.1038/srep43135
Recent papers Potent covalent inhibitors of bacterial urease identified by activity-reactivity profiling
Macegoniuk, K.; Kowalczyk, R.; Rudzińska, A.; Psurski, M.; Wietrzyk, J.; Berlicki, Ł. Bioorg. Med. Chem. Lett. 2017
, 1346DOI: 10.1016/j.bmcl.2017.02.022 Abstract
Covalent enzyme inhibitors constitute a highly important group of biologically active compounds, with numerous drugs available on the market. Although the discovery of inhibitors of urease, a urea hydrolyzing enzyme crucial for the survival of some human pathogens, is a field of medicinal chemistry that has grown in recent years, covalent urease inhibitors have been rarely investigated until now. Forty Michael acceptor-type compounds were screened for their inhibitory activities against bacterial urease, and several structures exhibited high potency in the nanomolar range. The correlation between chemical reactivity towards thiols and inhibitory potency indicated the most valuable compound — acetylenedicarboxylic acid, with View the MathML source = 42.5 nM and logkGSH = –2.14. Molecular modelling studies revealed that acetylenedicarboxylic acid is the first example of highly effective mode of binding based on simultaneous bonding to a cysteine residue and interaction with nickel ions present in the active site. Activity-reactivity profiling of reversible covalent enzyme inhibitors is a general method for the identification of valuable drug candidates.
Recent papers Controlling the Helix Handedness of ααβ-Peptide Foldamers through Sequence Shifting
Szefczyk, M.; Węglarz-Tomczak, E.; Fortuna, P.; Krzysztoń, A.; Rudzińska-Szostak, E.; Berlicki, Ł. Angew. Chem. Int. Ed. 2017
, 2087DOI: 10.1002/anie.201610154 Abstract
Peptide foldamers containing both cis-β-aminocyclopentanecarboxylic acid and α-amino acid residues combined in various sequence patterns (ααβ, αααβ, αβααβ, and ααβαααβ) were screened using CD and NMR spectroscopy for the tendency to form helices. ααβ-Peptides were found to fold into an unprecedented and well-defined 16/17/15/18/14/17-helix. By extending the length of the sequence or shifting a fragment of the sequence from one terminus to another in ααβ-peptides, the balance between left-handed and right-handed helix populations present in the solution can be controlled. Engineering of the peptide sequence could lead to compounds with either a strong propensity for the selected helix sense or a mixture of helical conformations of opposite senses.
Recent papers Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45)
Drag-Zalesinska M, Drag M, Poreba M, Borska S, Kulbacka J, Saczko J Cancer Cell International 2017
, 7DOI: 10.1186/s12935-016-0369-3
Recent papers Emerging challenges in the design of selective protease substrates, inhibitors and activity-based probes for indistinguishable proteases
Kasperkiewicz P, Poreba M, Groborz K, Drag M FEBS Journal 2017
, 10DOI: 10.1111/febs.14001
Recent papers Extended substrate specificity and first potent irreversible inhibitor/activity-based probe design for Zika virus NS2B-NS3 protease
Rut W, Zhang L, Kasperkiewicz P, Poreba M, Hilgenfeld R, Drag M Antiviral Research 2017
, 88DOI: 10.1016/j.antiviral.2016.12.018
Recent papers P-C bond formation in reactions of Morita-Baylis-Hillman adducts with phosphorus nucleophiles.
Talma, M.; Mucha, A. Arkivoc 2017
, 324DOI: 10.3998/ark.5550190.p009.787 Abstract
The Morita-Baylis-Hillman adducts (e.g., activated allyl acetates or bromides) are an unprecedented trifunctional synthetic platform for diverse types of nucleophilic displacements, additions and rearrangements. These reactions can proceed in an inter- and intra-molecular manner, and with a stereoselective induction. Accordingly, they contribute as the key steps to numerous synthetic pathways, including the total syntheses of natural products of a different class and origin and novel strategies leading to medicinally relevant compounds and commercialized drugs. The synthetic feasibility of the Morita-Baylis-Hillman adducts in organophosphorus chemistry has been explored to a relatively low extent. In this review, we summarize the current state of the art on the formation of the C-P bond by means of the title reactions. The scope of the processes, the stereochemistry of the products and their further synthetic relevance to obtain multifunctional compounds, including those that are biologically active, are summarized.