Publications by authors named "Beata Kolesinska"

55 Publications

1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors.

Molecules 2021 Jun 28;26(13). Epub 2021 Jun 28.

Department of Organic Chemistry, Medical University, Mickiewicza Street 2a, 15-222 Białystok, Poland.

A series of new analogs of nitrogen mustards (-) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and -secretase (BACE1) enzymes. The AChE inhibitory activity studies were carried out using Ellman's colorimetric method, and the BACE1 inhibitory activity studies were carried out using fluorescence resonance energy transfer (FRET). All compounds displayed considerable AChE and BACE1 inhibition. The most active against both AChE and BACE1 enzymes were compounds and , with an inhibitory concentration of AChE IC = 0.051 µM; 0.055 µM and BACE1 IC = 9.00 µM; 11.09 µM, respectively.
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http://dx.doi.org/10.3390/molecules26133942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271926PMC
June 2021

Synthesis of Isothiocyanates Using DMT/NMM/TsO as a New Desulfurization Reagent.

Molecules 2021 May 6;26(9). Epub 2021 May 6.

Faculty of Chemistry, Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25-97%). Synthesis was performed in a "one-pot", two-step procedure, in the presence of organic base (EtN, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72-96%). Isothiocyanate derivatives of L- and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on and bacterial strains, where the most active was ITC
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http://dx.doi.org/10.3390/molecules26092740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125326PMC
May 2021

Non-Aggregating Amylin Fragments as an Inhibitors of the Aggregation Process of Susceptible to Aggregation Fragments 18-22, 23-27, and 33-37 of Hormone.

Chem Biodivers 2021 Apr 9;18(4):e2100034. Epub 2021 Mar 9.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.

Amylin aggregation is one of the factors in the development of diabetes mellitus, which is classified as a civilization disease. The aim of this research was to find whether non-aggregating fragments 1-7, 8-12, 13-17 and 28-32 of amylin would inhibit the aggregation of the amyloidogenic cores 18-22, 23-27, 33-37 of hormone. In the study of the inhibitory potential of non-aggregating amylin fragments, a set of independent methods were used to study aggregation properties (spectroscopic and fluorescence studies with the use of indicators, microscopic studies, circular dichroism studies) and the method of prediction of aggregation properties. The performed research allowed to select the cyclic fragment (1-7) H-KCNTATC-OH with disulfide bond as an inhibitor capable of inhibiting the aggregation of all amyloidogenic cores 18-22, 23-27, 33-37 of the hormone. Additionally, it was found that this peptide inhibits insulin hot spot aggregation, which may indicate its universal utility in inhibiting the process of aggregation of hormones regulating carbohydrate metabolism directly related to the development of diabetes. Research on the possibility of the extensive use of the cyclic fragment (1-7) of H-KCNTATC-OH as a peptide inhibitor of the polypeptide/protein aggregation process is ongoing.
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http://dx.doi.org/10.1002/cbdv.202100034DOI Listing
April 2021

N-Methylated Analogs of hIAPP Fragments 18-22, 23-27, 33-37 Inhibit Aggregation of the Amyloidogenic Core of the Hormone.

Chem Biodivers 2021 Jan 17;18(1):e2000842. Epub 2020 Dec 17.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.

Amylin (hIAPP) aggregation leads to the formation of insoluble deposits and is one of the factors in the development of type II diabetes. The aim of this research was to find N-methylated analogs of the aggregating amylin fragments 18-22, 23-27, and 33-37, which would not themselves be susceptible to aggregation and would inhibit the aggregation of the amyloidogenic cores of the hormone. None of the analogs of fragment 18-22 containing one or two N-methylated amino acid residues showed any tendency to aggregate. Only the peptide H-F(N-Me)GA(N-Me) IL-OH (6) derived from the 23-27 hIAPP hot spot did not form fibrous structures. All analogs of the 33-37 amylin fragment were characterized by the ability to form aggregates, despite the presence of N-methylated amino acids in their structures. N-Methylated peptides 1-5 demonstrated inhibitory properties against the aggregation of fragment 18-22. Aggregation of the amyloidogenic core of 23-27 was significantly inhibited by N-methylated peptides 1-3 derived from the (18-22) H-HSSNN-OH fragment and by the H-F(N-Me)GA(N-Me)IL-OH (6) fragment derived from the 23-27 amylin hot spot. Fragment (33-37) H-GSNTY-NH was found to be inhibited in the presence of N-methylated peptides 1-3 derived from the 18-22 fragment and by the double methylated peptide H-F(N-Me)GA(N-Me)IL-OH (6). Research on the possibility of using N-methylated analogs of amyloidogenic amylin cores as inhibitors of hormone aggregation is ongoing, with a focus on finding the minimum concentration of N-methylated peptides capable of inhibiting the aggregation of hIAPP hot spots.
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http://dx.doi.org/10.1002/cbdv.202000842DOI Listing
January 2021

Human Serum Albumin Binds Native Insulin and Aggregable Insulin Fragments and Inhibits Their Aggregation.

Biomolecules 2020 09 25;10(10). Epub 2020 Sep 25.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

The purpose of this study was to investigate whether Human Serum Albumin (HSA) can bind native human insulin and its A13-A19 and B12-B17 fragments, which are responsible for the aggregation of the whole hormone. To label the hormone and both hot spots, so that their binding positions within the HSA could be identified, 4-(1-pyrenyl)butyric acid was used as a fluorophore. Triazine coupling reagent was used to attach the 4-(1-pyrenyl)butyric acid to the N-terminus of the peptides. When attached to the peptides, the fluorophore showed extended fluorescence lifetimes in the excited state in the presence of HSA, compared to the samples in buffer solution. We also analyzed the interactions of unlabeled native insulin and its hot spots with HSA, using circular dichroism (CD), the microscale thermophoresis technique (MST), and three independent methods recommended for aggregating peptides. The CD spectra indicated increased amounts of the α-helical secondary structure in all analyzed samples after incubation. Moreover, for each of the two unlabeled hot spots, it was possible to determine the dissociation constant in the presence of HSA, as 14.4 µM (A13-A19) and 246 nM (B12-B17). Congo Red, Thioflavin T, and microscopy assays revealed significant differences between typical amyloids formed by the native hormone or its hot-spots and the secondary structures formed by the complexes of HSA with insulin and A13-A19 and B12-B17 fragments. All results show that the tested peptide-probe conjugates and their unlabeled analogues interact with HSA, which inhibits their aggregation.
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http://dx.doi.org/10.3390/biom10101366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601681PMC
September 2020

New Human Islet Amyloid Polypeptide Fragments Susceptible to Aggregation.

Chem Biodivers 2020 Sep 8;17(9):e2000501. Epub 2020 Sep 8.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, Lodz, 90-924, Poland.

Human Islet Amyloid Polypeptide (hIAPP) plays a key role in the pathogenesis of type II diabetes. The aim of this research was to search for new amyloidogenic fragments of hIAPP. An initial attempt to predict the amyloidogenic cores of polypeptides/proteins using five different computer programs did not provide conclusive results. Therefore, we synthesized hIAPP fragments covering the entire hormone. The fragments were assessed for their aggregation ability, using recommended methods to search for the amyloidogenic fragments of the polypeptides/proteins. It was found that fragments (18-22) H-HSSNN-OH and (33-37) H-GSNTY-NH aggregate and form stable amyloid-like structures. Both of these fragments have a much higher antiproliferative activity relative to the RIN-5F cell compared to the (23-27) H-FGAIL-OH fragment widely regarded as the amyloidogenic core of amylin. The analog of (33-37) H-GSNTY-NH containing a free carboxy group on the C-terminal amino acid (H-GSNTY-OH) does not have amyloidogenic properties and can therefore be considered as a potential inhibitor of amylin aggregation. Research on the use of non-aggregating amylin fragments as potential hormone aggregation inhibitors is ongoing.
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http://dx.doi.org/10.1002/cbdv.202000501DOI Listing
September 2020

Conjugates of Chitosan and Calcium Alginate with Oligoproline and Oligohydroxyproline Derivatives for Potential Use in Regenerative Medicine.

Materials (Basel) 2020 Jul 10;13(14). Epub 2020 Jul 10.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

New materials that are as similar as possible in terms of structure and biology to the extracellular matrix (external environment) of cells are of great interest for regenerative medicine. Oligoproline and oligohydroxyproline derivatives (peptides -) are potential mimetics of collagen fragments. Peptides - have been shown to be similar to the model collagen fragment (H-Gly-Hyp-Pro-Ala-Hyp-Pro-OH, ) in terms of both their spatial structure and biological activity. In this study, peptides - were covalently bound to nonwovens based on chitosan and calcium alginate. Incorporation of the peptides was confirmed by Fourier transform -infrared (FT-IR) and zeta potential measurements. Biological studies (cell metabolic activity by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and Live/Dead assay) proved that the obtained peptide-polysaccharide conjugates were not toxic to the endothelial cell line EA.hy 926. In many cases, the conjugates had a highly affirmative influence on cell proliferation. The results of this study show that conjugates of chitosan and calcium alginate with oligoproline and oligohydroxyproline derivatives have potential for use in regenerative medicine.
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http://dx.doi.org/10.3390/ma13143079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412561PMC
July 2020

Biological Activity of Hydrophilic Extract of Grown on Post-Fermentation Leachate from a Biogas Plant Supplied with Stillage and Maize Silage.

Molecules 2020 Apr 14;25(8). Epub 2020 Apr 14.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

Algae are employed commonly in cosmetics, food and pharmaceuticals, as well as in feed production and biorefinery processes. In this study, post-fermentation leachate from a biogas plant which exploits stillage and maize silage was utilized as a culture medium for . The content of polyphenols in hydrophilic extracts of the biomass was determined, and the extracts were evaluated for their antioxidant activity (DPPH assay), antibacterial activity (against , , , ) and antifungal activity (against , , ). The use of the post-fermentation leachate was not found to affect the biological activity of the microalgae. The aqueous extract of biomass was also observed to exhibit activity against nematodes. The results of this study suggest that biomass cultured on post-fermentation leachate from a biogas plant can be successfully employed as a source of natural antioxidants, food supplements, feed, natural antibacterial and antifungal compounds, as well as in natural methods of plant protection.
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http://dx.doi.org/10.3390/molecules25081790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221910PMC
April 2020

Conjugates of Copper Alginate with Arginine-Glycine-Aspartic Acid (RGD) for Potential Use in Regenerative Medicine.

Materials (Basel) 2020 Jan 11;13(2). Epub 2020 Jan 11.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

Current restrictions on the use of antibiotics, associated with increases in bacterial resistance, require new solutions, including materials with antibacterial properties. In this study, copper alginate fibers obtained using the classic wet method were used to make nonwovens which were modified with arginine-glycine-aspartic acid (RGD) derivatives. Stable polysaccharide-peptide conjugates formed by coupling with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO), and materials with physically embedded RGD derivatives, were obtained. The materials were found to be characterized by very high antibacterial activity against and . Cytotoxicity studies confirmed that the materials are not cytotoxic. Copper alginate conjugates with RGD peptides have strong potential for use in regenerative medicine, due to their biocompatibility and innate antibacterial activity.
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http://dx.doi.org/10.3390/ma13020337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013949PMC
January 2020

Characteristic Features of Wound Dressings Based on Butyric-Acetic Chitin Copolyesters-Results of Clinical Trials.

Materials (Basel) 2019 Dec 12;12(24). Epub 2019 Dec 12.

Tricomed SA, Świętojańska Street 5/9, 93-493 Lodz, Poland.

The article presents the results of clinical trials of wound dressings whose main ingredient is butyric-acetic chitin copolyester (BAC 90:10). It is a chitin derivative soluble in typical organic solvents. During the trial, the dressings were used on wounds resulting from venous insufficiency or diabetes. The trial evaluated the safety of use and efficacy of three forms of the dressing including porous membrane (Medisorb R Membrane), porous membrane with silver (Medisorb R Ag), and powder (Medisorb R Powder). The clinical trial had a multi-centre character. Three medical units were engaged in the study. The trial included 36 patients (12 men and 24 women). The mean age of the participants was 65 years of age (age range: 26-96). The choice of dressings was made on the basis of preliminary evaluation of the wound, clinical signs of infection, or risk of infection. Medisorb R Membrane dressing was used in 23 patients, Medisorb R Ag dressing was used in 15 patients, and Medisorb R powder was used in two patients. During the course of the trial, there were 10 control visits planned. The obtained results prove the safety and efficacy of dressings in question. The efficacy of treatment was evaluated as good. In the majority of patients, the ulceration was decreased both on the surface and in depth. The success of the treatment relied not only on the applied dressing, but also the stage of the basic disease, the accompanying diseases, and the age of the patient.
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http://dx.doi.org/10.3390/ma12244170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947344PMC
December 2019

Insulin Hot-Spot Analogs Formed with -Methylated Amino Acid Residues Inhibit Aggregation of Native Hormone.

Molecules 2019 Oct 15;24(20). Epub 2019 Oct 15.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

In this study, -methylated analogs of hot-spots of insulin were designed and synthesized, in the expectation that they would inhibit the aggregation of both insulin hot-spots and the entire hormone. Synthesis of insulin "amyloidogenic" analogs containing -methylated amino acid residues was performed by microwave-assisted solid phase according to the Fmoc/tert-Bu strategy. As a coupling reagent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO) was used. Three independent methods were applied in aggregation studies of the complexes of insulin with its -methylated peptides. Additionally, circular dichroism (CD) measurements were used to confirm that aggregation processes did not occur in the presence of the -methylated analogs of hot-spot insulin fragments, and that insulin retains its native conformation. Of the seven -methylated analogs of the A- and B-chain hot-spots of insulin, six inhibited insulin aggregation (peptides and -). All tested peptides were found to have a lower ability to inhibit the aggregation of insulin hot-spots compared to the capability to inhibit native hormone aggregation.
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http://dx.doi.org/10.3390/molecules24203706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832904PMC
October 2019

Fibrous Aggregates of Short Peptides Containing Two Distinct Aromatic Amino Acid Residues.

Chem Biodivers 2019 Nov 25;16(11):e1900339. Epub 2019 Oct 25.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.

The aim of the study was the assessment of the ability of short peptides to form aggregates under physiological conditions. The dipeptides studied were derived from different aromatic amino acids (heteroaromatic peptides). Tripeptides were obtained from two distinct aromatic amino acids and cysteine or methionine residue in the C-terminal, N-terminal, or central position. The ability of the peptides to form fibrous aggregates under physiological conditions was evaluated using three independent methods: the Congo Red assay, the Thioflavin T assay, and microscopic examinations using normal and polarized light. Materials potentially useful for regenerative medicine were selected based on their cytotoxicity to the endothelial cell line EA.hy 926 and physicochemical properties of films formed by peptides. The required parameters of biocompatibility were fulfilled by H-PheCysTrp-OH, H-PheCysTyr-OH, H-PheTyrMet-OH, and H-TrpTyr-OH.
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http://dx.doi.org/10.1002/cbdv.201900339DOI Listing
November 2019

Synthesis and cellular effects of novel 1,3,5-triazine derivatives in DLD and Ht-29 human colon cancer cell lines.

Invest New Drugs 2020 08 13;38(4):990-1002. Epub 2019 Sep 13.

Department of Organic Chemistry, Medical University of Bialystok, Białystok, Poland.

This study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell lines. A novel series of 2,4,6-trisubstituted 1,3,5-triazine derivatives bearing 2-chloroethyl and oligopeptide moieties was designed and synthesized. The most cytotoxic derivative was triazine with an Ala-Ala-OMe substituent on the ring (compound 7b). This compound induced time- and dose-dependent cytotoxicity in the DLD-1 and HT-29 colon cancer cell lines. The triazine derivative furthermore induced apoptosis through intracellular signaling pathway attenuation. Compound 7b may be a candidate for further evaluation as a chemotherapeutic agent against colorectal cancer.
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http://dx.doi.org/10.1007/s10637-019-00838-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340680PMC
August 2020

Antimicrobial and Antibiofilm N-acetyl-L-cysteine Grafted Siloxane Polymers with Potential for Use in Water Systems.

Int J Mol Sci 2019 Apr 24;20(8). Epub 2019 Apr 24.

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland.

Antibiofilm strategies may be based on the prevention of initial bacterial adhesion, the inhibition of biofilm maturation or biofilm eradication. N-acetyl-L-cysteine (NAC), widely used in medical treatments, offers an interesting approach to biofilm destruction. However, many Eubacteria strains are able to enzymatically decompose the NAC molecule. This is the first report on the action of two hybrid materials, NAC-Si-1 and NAC-Si-2, against bacteria isolated from a water environment: , , , , and . The NAC was grafted onto functional siloxane polymers to reduce its availability to bacterial enzymes. The results confirm the bioactivity of NAC. However, the final effect of its action was environment- and strain-dependent. Moreover, all the tested bacterial strains showed the ability to degrade NAC by various metabolic routes. The NAC polymers were less effective bacterial inhibitors than NAC, but more effective at eradicating mature bacterial biofilms.
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http://dx.doi.org/10.3390/ijms20082011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515369PMC
April 2019

Search for New Aggregable Fragments of Human Insulin.

Molecules 2019 Apr 23;24(8). Epub 2019 Apr 23.

Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

In this study, three independent methods were used to identify short fragment of both chains of human insulin which are prone for aggregation. In addition, circular dichroism (CD) research was conducted to understand the progress of aggregation over time. The insulin fragments (deca- and pepta-peptides) were obtained by solid-phase synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TosO) as a coupling reagent. Systematic studies allowed identification of the new fragments, expected to be engaged in triggering aggregation of the entire structure of human insulin under physiological conditions. It was found that the aggregation process occurs through various structural conformers and may favor the formation of a fibrous structure of aggregate.
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http://dx.doi.org/10.3390/molecules24081600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514721PMC
April 2019

Influence of Porous Dressings Based on Butyric-Acetic Chitin Co-Polymer on Biological Processes In Vitro and In Vivo.

Materials (Basel) 2019 Mar 23;12(6). Epub 2019 Mar 23.

Department of Experimental Surgery and Biomaterial Research, Wroclaw Medical University, Bujwida Street 44, 50-368 Wroclaw, Poland.

In spite of intensively conducted research allowing for the development of more and more advanced wound dressing materials, there is still a need for dressings that stimulate not only reparative and regenerative processes, but also have a positive effect on infected and/or difficult-to-heal wounds. Porous dressing materials based on butyric-acetic chitin co-polyester containing 90% of butyryl and 10% of acetyl groups (BAC 90/10) can also be included in the group mentioned above. Two types of dressings were obtained by the salt leaching method, i.e. a porous sponge Medisorb R and Medisorb Ag with an antibacterial additive. The aim of the study was to evaluate biological effects of porous Medisorb R and Medisorb Ag dressings under in vitro and in vivo conditions. In an in vitro biodegradation test, no mass loss of Medisorb R dressing was observed within 14 days of incubation in physiological fluids at 37 °C. However, on the basis of the FTIR (Fourier Transform Infrared Spectroscopy) tests, surface degradation of Medisorb R dressing was observed. Additionally, the antibacterial activity of the porous Medisorb Ag dressing containing microsilver as an antibacterial additive was confirmed. The in vivo studies included inflammatory activity, skin irritation and sensitisation tests, as well an assessment of local effect after contact with subcutaneous tissue up to 6 months and skin wounds up to 21 days. In the in vivo tests, the dressings exhibited neither effects of skin irritation nor sensitisation. Under macroscopic examination, in full thickness defects of subcutaneous tissue and skin, the dressings caused wound healing with no inflammation, undergoing the most gradual biodegradation between weeks 4 and 8, and the observed differences were statistically significant. In the histological assessment, a weakened, limited inflammatory process associated with degradation of the material has been observed. The process of skin wound healing under Medisorb R dressing in the early period was accelerated compared to that observed in the control group with a gauze dressing.
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http://dx.doi.org/10.3390/ma12060970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471426PMC
March 2019

Butanol Synthesis Routes for Biofuel Production: Trends and Perspectives.

Materials (Basel) 2019 Jan 23;12(3). Epub 2019 Jan 23.

Institute of Fermentation Technology and Microbiology, Faculty of Biochemistry and Food Sciences, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland.

Butanol has similar characteristics to gasoline, and could provide an alternative oxygenate to ethanol in blended fuels. Butanol can be produced either via the biotechnological route, using microorganisms such as clostridia, or by the chemical route, using petroleum. Recently, interest has grown in the possibility of catalytic coupling of bioethanol into butanol over various heterogenic systems. This reaction has great potential, and could be a step towards overcoming the disadvantages of bioethanol as a sustainable transportation fuel. This paper summarizes the latest research on butanol synthesis for the production of biofuels in different biotechnological and chemical ways; it also compares potentialities and limitations of these strategies.
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http://dx.doi.org/10.3390/ma12030350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384976PMC
January 2019

Chitosan and Its Derivatives - Biomaterials with Diverse Biological Activity for Manifold Applications.

Mini Rev Med Chem 2019 ;19(9):737-750

Tricomed SA, ul. Swietojanska 5/9, 93-493 Lodz, Poland.

Derived from chitin, chitosan is a natural polycationic linear polysaccharide being the second most abundant polymer next to cellulose. The main obstacle in the wide use of chitosan is its almost complete lack of solubility in water and alkaline solutions. To break this obstacle, the structure of chitosan is subjected to modification, improving its physic-chemical properties and facilitating application as components of composites or hydrogels. Derivatives of chitosan are biomaterials useful for different purposes because of their lack of toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the methods of chemical modifications of chitosan which allow to obtain tailor- made properties required for a variety of biomedical applications. Selected pharmaceutical and biomedical applications of chitosan derivatives are also highlighted. Possibility to manage waste from arthropod and crab processing is also emphasized.
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http://dx.doi.org/10.2174/1389557519666190112142735DOI Listing
June 2019

The cellular effects of novel triazine nitrogen mustards in glioblastoma LBC3, LN-18 and LN-229 cell lines.

Invest New Drugs 2019 10 15;37(5):984-993. Epub 2019 Jan 15.

Department of Pharmaceutical Biochemistry, Medical University of Bialystok, Bialystok, Poland.

1,3,5-triazine is an important heterocyclic skeleton for mono, two or three 2-chloroethylamine groups. The study presented here provides novel information on cellular effects of 1,3,5-triazine with mono, two or three 2-chloroethylamine groups in glioblastoma LBC3, LN-18 and LN-229 cell lines. In our study, the most cytotoxic effect was observed in 1,3,5-triazine with three 2-chloroethylamine groups (12f compound). It has been demonstrated that 12f induce time- and dose-dependent cytotoxicity in all investigated glioma cell lines. Apart from that in glioblastoma cells, treated with 12f compound, we noticed strong induction of apoptosis. In conclusion, this research provides novel information concerning cellular effects of apoptosis in LBC3, LN-18 and LN-229 cell lines. Moreover, we suggest that 12f compound may be a candidate for further evaluation as an effective chemotherapeutic agent for human glioblastoma cells.
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http://dx.doi.org/10.1007/s10637-018-0712-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736897PMC
October 2019

Examination of THPC as an oxygen scavenger impacting VIC dosimeter thermal stability and comparison of NVP-containing polymer gel dosimeters.

Phys Med Biol 2019 01 31;64(3):035019. Epub 2019 Jan 31.

Institute of Materials Science and Engineering, Lodz University of Technology, Lodz, Poland.

This work reports on the impact of tetrakis(hydroxymethyl)phosphonium chloride (THPC) on the properties of a VIC gel dosimeter (VIC is an abbreviated acronym of VIPAR). THPC was used as a substitute oxygen scavenger in VIC (17% N-vinylpyrrolidone, 8% N,N'-methylenebisacrylamide, 12% tert-butyl alcohol, 7.5% gelatine, 0.02% hydroquinone and an oxygen scavenger of 0.007% ascorbic acid and 0.0008% CuSO  ×  5HO). THPC reduced the gelation time of VIC from hours to minutes. The best composition (VIC-T) contained 14 mM THPC and a reduced gelatine concentration (5%) with respect to VIC, which allowed for gelation in about 3 min. VIC-T was characterised by the same dose sensitivity (0.176  ±  0.003 Gy s for VIC-T and 0.171  ±  0.002 Gy s for VIC), dose threshold (0.5 Gy) and dynamic dose range (0.5‒50 Gy) as VIC, and a lower linear dose range (20 Gy for VIC-T, 30 Gy for VIC) (0.47 T NMR measurements). VIC-T was stable for at least 10 days after irradiation, and 3D dose distribution was stable for over 4 months after irradiation. The dose response of VIC-T was independent of the radiation dose rate, type and energy of radiation for 6 and 15 MV photons and 12 MeV electrons. This is an improvement with respect to VIC which showed a different dose response for 6 MV photons than for 12 MeV electrons and 15 MV photons. Raman spectroscopy showed similarity in the rate of radiation-induced conversion of monomers in VIC and VIC-T, indicating interaction of THPC with gelatine in VIC-T, and showed ageing of gelatine in both dosimeters. Differential scanning calorimetry showed VIC-T stability at 0 °C-80 °C (VIC: 0 °C‒29.5 °C). The chemical polymerisation and crosslinking of gelatine with THPC is reported, the mechanism of which was analysed in detail. A comparison of N-vinylpyrrolidone-containing dosimeters is presented in this work.
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http://dx.doi.org/10.1088/1361-6560/aafa86DOI Listing
January 2019

Study on the Materials Formed by Self-Assembling Hydrophobic, Aromatic Peptides Dedicated to Be Used for Regenerative Medicine.

Chem Biodivers 2019 Mar 26;16(3):e1800543. Epub 2019 Feb 26.

Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.

The aims of this study were to identify the short aromatic peptides which are able to form highly ordered amyloid-like structures in self-assembling processes, to test the influence of length of hydrophobic peptides on tendency to aggregation, and to check if aggregated peptides fulfill requirements expected for materials useful for scaffolding. All tested hydrophobic peptides were prepared on solid phase by using DMT/NMM/TsO as a coupling reagent. The progress of aggregation was studied by set of independent tests. All aggregated peptides were found stable under in vitro conditions. All fibrous material formed by self-assembling of peptides does not show any cytotoxic effects on L929 fibroblast cells. Peptides containing tyrosine and tryptophan residues even effectively accelerated the proliferation and stimulated the activity of L929 fibroblasts.
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http://dx.doi.org/10.1002/cbdv.201800543DOI Listing
March 2019

Preparation Method of Porous Dressing Materials Based on Butyric-Acetic Chitin Co-Polyesters.

Materials (Basel) 2018 Nov 23;11(12). Epub 2018 Nov 23.

Tricomed S.A., Lodz, Swietojanska 5/9, 93-493 Lodz, Poland.

A method for obtaining highly porous materials in the form of film, based on the butyric-acetic chitin co-polyesters, containing 90% of butyryl and 10% of acetyl groups, was developed. The highly porous films, with thickness up to 0.11 mm, were obtained by two methods: (a) pouring 5% BAC 90/10 solution in ethanol on the layer of solid salts (porophor agent) which after solidification was eluted with water; (b) application of the suspension of porophor agent in BAC 90/10 solution in the solvent mixture with density similar to bulk porophor agent. In the final stage, the materials were obtained with porosity up to 95⁻99% and tensile strength 5 cN, which can be used as an active layer of medical dressings. The optimised procedure was used in the production of porous medical dressings (Medisorb) on an industrial scale. In the industrial method, NaCl was used as a porophor agent in the solid form and as a 3% solution in polymer. The final materials were characterised by porosity and other functional parameters at the level recommended for medical dressings. Medisorb series materials do not show in vitro cytotoxic activity.
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http://dx.doi.org/10.3390/ma11122359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317001PMC
November 2018

Orthogonal Functionalization of Nanodiamond Particles after Laser Modification and Treatment with Aromatic Amine Derivatives.

Nanomaterials (Basel) 2018 Nov 5;8(11). Epub 2018 Nov 5.

Institute of Materials Science and Engineering, Lodz University of Technology, Stefanowskiego 1/15, 90-924 Lodz, Poland.

A laser system with a wavelength of 1064 nm was used to generate sp² carbon on the surfaces of nanodiamond particles (NDPs). The modified by microplasma NDPs were analysed using FT-IR and Raman spectroscopy. Raman spectra confirmed that graphitization had occurred on the surfaces of the NDPs. The extent of graphitization depended on the average power used in the laser treatment process. FT-IR analysis revealed that the presence of C=C bonds in all spectra of the laser-modified powder. The characteristic peaks for olefinic bonds were much more intense than in the case of untreated powder and grew in intensity as the average laser power increased. The olefinized nanodiamond powder was further functionalized using aromatic amines via in situ generated diazonium salts. It was also found that isokinetic mixtures of structurally diverse aromatic amines containing different functional groups (acid, amine) could be used to functionalize the surfaces of the laser-modified nanoparticles leading to an amphiphilic carbon nanomaterial. This enables one-step orthogonal functionalization and opens the possibility of selectively incorporating molecules with diverse biological activities on the surfaces of NDPs. Modified NDPs with amphiphilic properties resulting from the presence carboxyl and amine groups were used to incorporate simultaneously folic acid (FA-CONH-(CH₂)₅-COOH) and 5(6)-carboxyfluorescein (FL-CONH-(CH₂)₂-NH₂) derivatives on the surface of material under biocompatible procedures.
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http://dx.doi.org/10.3390/nano8110908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266277PMC
November 2018

Analysis of structure and properties of antibacterial vascular patch used in abdominal aorta aneurysm surgeries.

J Appl Biomater Funct Mater 2019 Apr-Jun;17(2):2280800018793818. Epub 2018 Sep 3.

2 Tricomed SA, Lodz, Poland.

Background: Biocompatible materials are used for treatment of blood circulatory system diseases, especially abdominal aortic aneurysms. The most popular and often used are knitted and polymer vascular patches. The aim of this study was to optimize the manufacturing process of implantable materials, ensuring antibacterial activity useful for treating abdominal aorta aneurysms.

Methods: The vascular patch was manufactured from Trevira® yarn. The parameters of the intermediate product and vascular patch were tested according to standard procedures.

Results: The vascular patch, manufactured from microsilver-containing yarn, with crimps on the surface of the patch, has been found useful for treatment of abdominal aorta aneurysms. Introducing crimps on the surface of the patch resulted in reduction of water permeability and enabled cutting of the graft at various angles without fraying at the cut ends of the biomaterial. The final vascular patch was marked by a gradual release of silver within 48 hours.

Conclusions: On the basis of the performed test, it has been demonstrated that an implantable material for the treatment of abdominal aorta aneurysms was obtained, and that it can be considered as an alternative for currently used vascular patches. The final vascular patch was marked by a gradual release of silver during the first period of incubation. The antibacterial properties of the final product were confirmed by observation of a significant reduction in the number of and bacterial colonies.
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http://dx.doi.org/10.1177/2280800018793818DOI Listing
December 2019

Towards Intelligent Drug Design System: Application of Artificial Dipeptide Receptor Library in QSAR-Oriented Studies.

Molecules 2018 Aug 6;23(8). Epub 2018 Aug 6.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia.

The pharmacophore properties of a new series of potential purinoreceptor (P2X) inhibitors determined using a coupled neural network and the partial least squares method with iterative variable elimination (IVE-PLS) are presented in a ligand-based comparative study of the molecular surface by comparative molecular surface analysis (CoMSA). Moreover, we focused on the interpretation of noticeable variations in the potential selectiveness of interactions of individual inhibitor-receptors due to their physicochemical properties; therefore, the library of artificial dipeptide receptors (ADP) was designed and examined. The resulting library response to individual inhibitors was arranged in the array, preprocessed and transformed by the principal component analysis (PCA) and PLS procedures. A dominant absolute contribution to PC1 of the Glu attached to heptanoic gating acid and Phe bonded to the linker -phenylenediamine/triazine scaffold was revealed by the PCA. The IVE-PLS procedure indicated the receptor systems with predominant Pro bonded to the linker and Glu, Gln, Cys and Val directly attached to the gating acid. The proposed comprehensive ligand-based and simplified structure-based methodology allows the in-depth study of the performance of peptide receptors against the tested set of compounds.
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http://dx.doi.org/10.3390/molecules23081964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222794PMC
August 2018

Search for Fibrous Aggregates Potentially Useful in Regenerative Medicine Formed under Physiological Conditions by Self-Assembling Short Peptides Containing Two Identical Aromatic Amino Acid Residues.

Molecules 2018 Mar 2;23(3). Epub 2018 Mar 2.

Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

This study investigates the propensity of short peptides to self-organize and the influence of aggregates on cell cultures. The dipeptides were derived from both enantiomers of identical aromatic amino acids and tripeptides were prepared from two identical aromatic amino acids with one cysteine or methionine residue in the C-terminal, N-terminal, or central position. The formation or absence of fibrous structures under physiological conditions was established using Congo Red and Thioflavine T assays as well as by microscopic examination using normal and polarized light. The in vitro stability of the aggregates in buffered saline solution was assessed over 30 days. Materials with potential for use in regenerative medicine were selected based on the cytotoxicity of the peptides to the endothelial cell line EA.hy 926 and the wettability of the surfaces of the films, as well as using scanning electron microscopy. The criteria were fulfilled by H-PhePhe-OH, H-CysPhePhe-OH, H-CysTyrTyr-OH, H-PhePheCys-OH, H-TyrTyrMet-OH, and H-TyrMetTyr-OH. Our preliminary results suggest that the morphology and cell viability of L919 fibroblast cells do not depend on the stereochemistry of the self-organizing peptides.
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http://dx.doi.org/10.3390/molecules23030568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017032PMC
March 2018

Cross-Reactivity of Polyclonal Antibodies against Canavalia ensiformis (Jack Bean) Urease and Helicobacter pylori Urease Subunit A Fragments.

Chem Biodivers 2018 Jan 27;15(1). Epub 2017 Dec 27.

Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 94-050, Lodz, Poland.

Overlapping decapeptide fragments of H. pylori urease subunit A (UreA) were synthesized and tested with polyclonal antibodies against Canavalia ensiformis (Jack bean) urease. The linear epitopes of UreA identified using the dot blot method were then examined using epitope mapping. For this purpose, series of overlapping fragments of UreA, frameshifted ± four amino acid residues were synthesized. Most of the UreA epitopes which reacted with the Jack bean urease polyclonal antibodies had been recognized in previous studies by monoclonal antibodies against H. pylori urease. Fragments 11 - 24, 21 - 33, and 31 - 42 were able to interact with the Jack bean urease antibodies, giving stable immunological complexes. However, the lack of recognition by these antibodies of all the components in the peptide map strongly suggests that a non-continuous (nonlinear) epitope is located on the N-terminal domain of UreA.
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http://dx.doi.org/10.1002/cbdv.201700444DOI Listing
January 2018

Synthesis and biological activity of cyclolinopeptide A analogues modified with γ-bis(homo-phenylalanine).

Bioorg Med Chem 2017 08 2;25(16):4265-4276. Epub 2017 Jun 2.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland.

Cyclolinopeptide A (CLA), an immunosuppressive nonapeptide derived from linen seeds, was modified with S or R-γ-bis(homo-phenylalanine) in positions 3 or 4, or both 3 and 4. These modifications changed the flexibility of new analogues and distribution of intramolecular hydrogen bonds. Analogues 11 c(Pro-Pro-Phe-S-γ-hhPhe-Leu-Ile-Ile-Leu-Val), 13 c(Pro-Pro-S-γ-hhPhe-R-γ-hhPhe-Leu-Ile-Ile-Leu-Val) and 15 c(Pro-Pro-R-γ-hhPhe-Phe-Leu-Ile-Ile-Leu-Val) existed as a mixture of stable cis/trans isomers of Pro-Pro peptide bond. The comparison of the relative spatial orientations in crystal state of the two carbonyl groups, neighboring γ-amino acids, revealed conformational similarities to α-peptides. The addition of two -CH- groups in γ-amino acids led to a more rigid conformation, although a more flexible one was expected. A significant difference in the relative orientation of the carbonyl groups was found for cyclic γ-peptides with a dominance of an antiparallel arrangement. As carbonyl groups may be engaged in the interactions with plausible receptors through hydrogen bonds, a similar biological activity of the modified peptides was expected. Our biological studies showed that certain cyclic, but not the corresponding linear peptides, lowered the viability of peripheral blood mononuclear cells (PBMC) at 100μg/mL concentration. The proliferation of PBMC induced by phytohemagglutinin A (PHA) was strongly inhibited by cyclic peptides only, in a dose-dependant manner. On the other hand, lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) production in whole blood cell cultures was inhibited by both linear and cyclic peptides. Peptide 15 c(Pro-Pro-R-γ-hhPhe-Phe-Leu-Ile-Ile-Leu-Val) blocked the expression of caspase-3, inhibited the expression of caspases-8 and -9 in 24h culture of Jurkat cells, and caused DNA fragmentation in these cells, as an indicator of apoptosis. Thus, we revealed a new mechanism of immunosuppressive action of a nonapeptide.
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http://dx.doi.org/10.1016/j.bmc.2017.05.063DOI Listing
August 2017

The quest for the shortest fragments of A (13-19) and B (12-17) responsible for the aggregation of human insulin.

Nanomedicine (Lond) 2016 08 27;11(16):2083-101. Epub 2016 Jul 27.

Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.

Aim: To identify the shortest components of A13-A19, B12-B17 fragments capable for fibrillation and to validate the dependability of aggregation on the presence of hydroxyl group engaged in the 'tyrosine kissing'.

Materials & Methods: Fragments A13-A19 and B12-B17 of insulin and all shortened analogues were obtained by using DMT/NMM/TosO(-) as a coupling reagent. The aggregation was studied by three independent tests.

Results: Studies on the susceptibility to aggregation of truncated analogs of insulin amyloidogenic core show three groups of peptides.

Conclusion: Truncation of A13-A419 fragment shows that fibrous structures are formed by all peptides bearing (13)H-LeuTyr-OH(14). Propensity to aggregation was found for (16)H-TyrLeu-OH(17) B12-B17 fragment. Tyrosine residue modification by incorporation of tert-butyl group on hydroxyl function gave analogues still predisposed to aggregation.
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http://dx.doi.org/10.2217/nnm-2016-0100DOI Listing
August 2016

Visible-Light Microscopic Discovery of Up to 150 μm Long Helical Amyloid Fibrils Built of the Dodecapeptide H-(Val-Ala-Leu) -OH and of Decapeptides Derived from Insulin.

Chem Biodivers 2016 Sep 31;13(9):1111-1117. Epub 2016 Aug 31.

Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH-Zürich, Hönggerberg HCI, Vladimir-Prelog-Weg 3, CH-8093, Zürich.

In the formation of amyloid fibrils from small peptides, the appearance of superhelices of (P)- or (M)-helicity has been observed for the first time; high concentrations of the peptides and extended periods of incubation at physiological pH appear to be important for this phenomenon. In view of the general importance of peptide and protein aggregation, we give a brief overview with selected examples for demonstration.
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http://dx.doi.org/10.1002/cbdv.201600167DOI Listing
September 2016
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