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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.


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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, accepted.
DOI: 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, 56, 2087
DOI: 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, 1
DOI: 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, 1
DOI: 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, 1
DOI: 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, 2017, 324
DOI: 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.

Recent papers

Synthesis, lipase catalyzed kinetic resolution, and determination of the absolute configuration of enantiomers of the Morita-Baylis-Hillman adduct 3-hydroxy-2-methylenebutanenitrile
Strub, D.J., Garboś, A., Lochyński, S.
ARKIVOC 2017, 313
DOI: 10.3998/ark.5550190.p009.749

Abstract
3(RS)-Hydroxy-2-methylenebutanenitrile was synthesized from acetaldehyde and acrylonitrile with DABCO as a catalyst. Optimization of the reaction conditions was conducted due to the fact that some literature procedures were not reproducible. Asymmetric transesterification of Morita-Baylis-Hillman adduct was carried out using 10 lipases. Hydroxynitrile was also esterified chemically and subjected to enzymatic hydrolysis with the same set of enzymes. The best results were obtained with lipase from Candida antarctica and Novozyme 435. Absolute configuration of an optically pure hydroxynitrile was determined by Mosher’s method.

Recent papers

Diethyl boronobenzylphosphonates as substrates in Petasis reactions
Rydzewska, A.; Olender, A.; Mucha, A.; Kafarski, P.
ARKIVOC 2017, 2017, 107
DOI: org/10.3998/ark.5550190.p009.740

Abstract
The Petasis reaction of alpha-(N"benzylamino)boronobenzylphosphonates with amines and salicylaldehyde or glyoxalic acid gives the desired products in moderate yields. The efficiency of the reaction is strongly dependent on the structure of the amine.

Recent papers

Phytotoxicity of aminobisphosphonates targeting both δ1-pyrroline-5-carboxylate reductase and glutamine synthetase
Giberti, S.; Bertazzini, M.; Liboni, M.; Berlicki, Ł.; Kafarski, P.; Forlani, G.
Pest Manag. Sci. 2017, 72, 435
DOI: 10.1002/ps.4299

Abstract
BACKGROUND Dual-target inhibitors may contribute to the management of herbicide-resistant weeds and avoid or delay the selection of resistant biotypes. Some aminobisphosphonates inhibit the activity of both glutamine synthetase and δ1-pyrroline-5-carboxylate (P5C) reductase in vitro, but the relevance of the latter in vivo has yet to be proven. This study aimed at demonstrating that these compounds can also block proline synthesis in planta.

RESULTS Two aminophosphonates, namely 3,5-dichlorophenylamino-methylenebisphosphonic acid and 3,5-dibromophenylaminomethylenebis phosphonic acid (Br2PAMBPA), showed inverse effectiveness against the two partially purified target enzymes from rapeseed. The compounds showed equipotency in inhibiting the growth of rapeseed seedlings and cultured cells. The analysis of amino acid content in treated cells showed a strong reduction in glutamate and glutamate-related amino acid pools, but a milder effect on free proline. In the case of Br2PAMBPA, toxic P5C levels accumulated in treated seedlings, proving that the inhibition of P5C reductase takes place in situ.

CONCLUSIONS Phenyl-substituted aminobisphosphonates may be regarded as true dual-target inhibitors. Their use to develop new active principles for crop protection could consequently represent a tool to address the problem of target-site resistance among weeds. © 2016 Society of Chemical Industry

Recent papers

Enzyme-mediated protoplast formation of Cuninghamella echinulata - preliminary studies.
Brzezińska-Rodak M, Klimek-Ochab M, Żymańczyk-Duda E
BioTechnologia 2016, 97, 27