Institute of Organic Chemistry I-32
Head of the unit:
Prof. dr hab. inż. Beata Kolesińska
Potential promoters:
Prof. dr hab. inż. Beata Kolesińska
Dr hab. inż Justyna Frączyk
Contact person:
Beata Kolesińska, Tel: 48-42-631-32-61, beata.kolesinska@p.lodz.pl
Scope of activities:
The main research area of the team includes:
- Searching for peptides/fragments of biologically active proteins useful in medicine,
- Functionalization of solid materials, nanomaterials, nanoparticles with peptides - transmitting and/or modulating the intended biological activity,
- Designing peptide/protein and hybrid materials useful in medicine,
- Materials and methods useful in medical diagnostics.
Present activities:
The research topics carried out concern:
- synthesis of polysaccharide-peptide materials influencing all stages of wound healing
- developing methods of obtaining hybrid materials useful in the regeneration of bone/cartilage tissue
- design and synthesis of multifunctional nanomaterial conjugates with peptides useful in diagnostics, therapy, and prognosis of neoplastic diseases
- developing methods of obtaining carbon nanomaterials with antimicrobial properties
- proteomic/metabolomic research on the diagnosis of cardiovascular diseases and neoplastic diseases - searching for new biomarkers
- developing methods for isolating compounds from biomass and transforming them into the use of valuable green chemicals
Future activities:
- research on the development of new biosensors for viral/bacterial infections based on the analysis of volatile compounds
- research on the use of HSA or other proteins as intelligent drug delivery systems
- development of new functionalized materials containing biologically active peptides useful as transdermal drug carriers with a peptide structure
- new hybrid materials containing fragments of proteins that are key to inhibiting the process of fibrosis and conditioning the regeneration process
Publications/patents, awards, projects:
- M. Kolasa, G. Galita, I. Majsterek, E. Kucharska, K. Czerczak, J. Wasko, A. Becht, J. Fraczyk, A. Gajda, L. Pietrzak, L. Szymanski, A. Krakowiak, Z. Draczynski, B. Kolesinska, Screening of Self-Assembling of Collagen IV Fragments into Stable Structures Potentially Useful in Regenerative Medicine, Int. J. Mol. Sci. 2021, 22, 13584.
- J. Frączyk, A. Rosowski, B. Kolesinska, A. Koperkiewcz, A. Sobczyk-Guzenda, Z.J. Kaminski, M. Dudek, Orthogonal Functionalization of Nanodiamond Particles after Laser Modification and Treatment with Aromatic Amine Derivatives. Nanomaterials 2018, 8, 908.
- Method of modifying carbon nanomaterials containing carboxyl groups on the surface, Patent no. P-419358.
Ongoing projects:
- Innovative hybrid materials useful in the preparation of dressings for the treatment of the diabetic foot, NCN, UMO2018/31/B/ST8/02760
- Influence of hybrid carbon structures on the process of regeneration of cartilage/bone tissue, NCN, UMO2018/31/B/ST8/02418
- Hemostatic, dual-use resorbable dressings, NCBiR, POIR.04.01.02-00-0004 / 17
Keywords:
peptide/protein materials, hybrid materials, regenerative medicine, peptide-functionalized nanomaterials, theranostics, medical diagnostics based on proteomics and metabolomics, anti-cancer compounds, peptide/protein aggregation, hybrid drug delivery systems, valuable compounds from biomass
List of internship proposal in this research team:
Postdoctoral internships, internships for PhD students and second-cycle students in research projects concerning: new materials functionalized with peptides/protein fragments useful in regenerative medicine, including the regeneration of fibrotic organs/tissues, solid materials (nanomaterials) meeting the assumptions of theranostics (cancer diseases, civilization diseases) , sensors/biosensors for the analysis of volatile compounds characteristic of pathogen infections, methods and diagnostic tools (biomarkers, chips).
The portfolio of research groups was created as part of the Programme "STER" – Internationalisation of doctoral schools” as part of the realization of the project “Curriculum for advanced doctoral education & taining – CADET Academy of Lodz University of Technology”.
Institute of Organic Chemistry I-32
Head of the unit:
Professor Elżbieta Sochacka
Potential promoters:
Grazyna Leszczynska, PhD, DSc, Associate Professor
Contact person:
Grazyna Leszczynska, PhD, DSc, tel: 42-631-31-50, grazyna.leszczynska@p.lodz.pl
Scope of activities:
- Modified RNA nucleosides: synthesis, physicochemical and structural properties . Changes in the chemical status of modified nucleosides under stressful conditions of the cell.
- Synthesis of model RNA and DNA oligomers for the study of cellular processes and the selection of inhibitors of pathogen replication.
- Research on the molecular causes of human diseases based on the DNA or RNA damage/mutation
- Epigenetic RNA modifications as an element of regulation of gene expression.
- The role of post-transcriptional modifications in the control of gene expression in tumor cells
- In vitro studies of the biological activity of the enzymes with increased expression in the tumor cells.
- Development of sequencing methods for modified tRNA molecules
Present activities:
- Study of the physicochemical and structural properties of pathogenic mttRNAs bearing methionine to determine the molecular reasons of mitochondrial dysfunction enhancing symptoms of hypertension, type 2 diabetes and Leber's Hereditary Optic Neuropathy (LHON). In addition, a protocol for the synthesis of 5-formylcytidine (f5C) modified oligoribonucleotides has been developed.
- Biological role of wobble selenonucleosides in bacterial tRNAs specific for Lys and Glu. This project requires the synthesis of 5-methylaminomethyl-2- selenouridine modified RNA oligomer (mnm5Se2U) and the study of CD and thermodynamic stability of the homoduplexes.
- Structural studies of oligomers containing newly discovered modified ribonucleosides: S-geranyl-2-thiouridine (geS2U) and cyclic 6- threonylcarbamoyl adenosine (ct6A)in the tRNA anticodon loop.
- Development of new, effective protocols for the synthesis of natural modified ribonucleosides, including t6A, 5-substituted uridines, 2- thiouridines, 2-selenouridines, 5-substituted cytidines. Studies of physicochemical and structural properties of nucleosides.
- Determination of the reactivity of 2-thio and 2-selenouridines with hydrogen peroxide as a factor that mimics oxidative stress in the cell
Future activities:
- Studies on the regulatory role of epigenetic modifications of mRNA, namely 5-methylcytidine (m5C), 5- hydroxymethylcytidine (hm5C), 5-formylcytidine (f5C) and 5-carboxymethylcytidine (ca5C) on the translation process.
- In vitro studies of the 5-hydroxymethylcytidine-RNA metabolism pathway mediated by A3A and hSMUG1 enzymes which show increased expression in tumor cells.
- Research on the usefulness of new precursor compounds in the preparation of modified nucleosides.
- Study of the influence of 2-thiocytidine methylation on the translation process in bacterial tRNA molecules bearing arginine.
Keywords:
modified tRNA nucleoside, modified oligoribonucleotides, anticodon arm, synthesis of RNA by phosphoramidite chemistry on solid-phase, biological activity of RNA
List of internship proposal in this research team:
Melanie Etheve-Quelquejeu, University Paris Descartes Ronald Micura, University of Innsbruck
List of attachments:
Publikacions from the last 3 years :
- Skotnicki, K., Janik, I., Sadowska, K., Leszczynska, G., Bobrowski, K. Radiation-Induced Oxidation Reactions of 2- Selenouracil in Aqueous Solutions: Comparison with Sulfur Analog of Uracil. Molecules 2022, 27(1), 133.
- Zhou J, Lénon M, Ravanat JL, Touati N, Velours C, Podskoczyj K, Leszczynska G, Fontecave M, Barras F, GolinelliPimpaneau B “Iron-sulfur biology invades tRNA modification: the case of U34 sulfuration”. Nucleic Acids Res. 2021;49, 997-4007.
- Leszczynska G, Cypryk M, Gistynski B, Sadowska K, Herman P, Bujacz G, Lodyga-Chruscinska E, Sochacka E, Nawrot B. “C5-substituted 2-selenouridines ensure efficient base pairing with guanosine; consequences for reading the NNG3’ synonymous mRNA codons”, Int. J. Mol. Sci. 2020, 21, 2882-2905;
- Bartosik K, Debiec K, Czarnecka A, Sochacka E, Leszczynska G. „Synthesis of nucleobase-modified RNA oligonucleotides by post-synthetic approach”, Molecules, 2020, 25, 3344-3381;
- Kulik K, Sadowska K, Wielgus E, Pacholczyk-Sienicka B, Sochacka E, Nawrot B “Different Oxidation Pathways of 2- Selenouracil and 2-Thiouracil, Natural Components of Transfer RNA”, Int J Mol Sci., 2020; 21(17), 5956.
- Debiec K, Matuszewski M, Podskoczyj K, Leszczynska G, Sochacka E. „Chemical synthesis of oligoribonucleotide (ASL of tRNALys T.brucei) containing a recently discovered cyclic form of 2-methylthio-N6-threonylcarbamoyladenosine (ms2ct6A).” Chem. Eur. J. 2019, 25, 13309-13317;
- Borowski R, Dziergowska A, Sochacka E, Leszczynska G. „Novel entry to the synthesis of (S)- and (R)-5- methoxycarbonylhydroxymethyluridines – diastereomeric pair of wobble tRNA nucleosides”, RSC Adv., 2019, 9, 40507- 40512.
Scientific projects:
- OPUS 13; NCN „Synthesis and structural studies of oligonucleotides with tRNA anticodon arm containing new modified nucleosides: ct6A, ms2ct6A, ges2U ”; term from 21.02. 2018 to 20.02.2022 No. UMO-2017/25/B/ST5/00971;
- OPUS 15 NCN „ Why did Nature introduce selenium to nucleosides at the wobble position of bacterial tRNAs?", term from 24.01.2019 to 24.01.2023. No 2018/29/B/ST5/02509; formal agreement No. 1/2019 was written between the Institute of Organic Chemistry of the Lodz University of Technology and CBMIM PAN in Lodz, represented by professor Barbara Nawrot.
The portfolio of research groups was created as part of the Programme "STER" – Internationalisation of doctoral schools” as part of the realization of the project “Curriculum for advanced doctoral education & taining – CADET Academy of Lodz University of Technology”.
Institute of Organic Chemistry I-32
Head of the unit:
Katarzyna Błażewska, Ph.D., D.Sc., TUL Prof
Potential promoters:
Katarzyna Błażewska, Ph.D., D.Sc., TUL Prof.
Joanna Małolepsza, Ph.D (auxiliary promoter)
Contact person:
Katarzyna Błażewska, Ph.D., D.Sc., TUL Prof, phone: 48-42-631-32-27, katarzyna.blazewska@p.lodz.pl
Scope of activities:
The main areas of interest and research directions:
- design and synthesis of new Rab geranylgeranyl transferase (RGGT) inhibitors derived from α-phosphonocarboxylates – structure-activity relationship studies;
- identification of the place of interaction of inhibitors with proteins in the cell - "affinity-based protein profiling";
- design and synthesis of inhibitors that induce proteolysis of desired protein – PROTAC;
- dual inhibitors of RGGT;
Present activities:
The main goal of our group is to develop new strategies towards controlling the potency of important class of enzymes, Rab GTPases (Rab proteins, Rabs), which are implicated in a number of human diseases, including cancer, neurodegenerative disorders and infections.
In order to be functional, Rab proteins are undergoing post-translational modification by introduction of lipophilic residues. This process is catalyzed by Rab geranylgeranyl transferase (RGGT). Its inhibition provides one of the ways to control the activity of Rab proteins. Thus, we are now interested in developing new inhibitors of RGGT with improved activity and selectivity. We also synthesize probes, in order to identify the place of interaction with RGGT and potential off-targets of phosphonocarboxylates.
Our recent interest is the development of bifunctional compounds that bear RGGTtargeting warhead combined with an inhibitor/ligand of a different protein. These two fragments are connected using appropriate linker. Such compounds can act as dual inhibitors and increase biological response.
Compounds designed and synthesized in our group are tested for their biological activity in the group of Prof. Edyta Gendaszewska-Darmach from Faculty of Biotechnology and Food Sciences, TUL).
Future activities:
Design and synthesis of peptide-based inhibitors of protein-protein interactions, which lead to selective regulation of Rabs.
Publications/ patents/ awards, grants: Selected publications:
- D. Kusy, A. Marchwicka, J. Małolepsza, K. Justyna, E. Gendaszewska-Darmach, K.M Błażewska Front. Chem. 2021, 8:596162;
- Kaźmierczak, D. Kusy, S. P. Niinivehmas, J. Gmach, Ł. Joachimiak, O. T. Pentikäinen, E. Gendaszewska-Darmach, K. M. Błażewska J. Med. Chem. 2017, 60, 8781.
- E. Gendaszewska-Darmach, M.A. Garstka, K.M Błażewska J. Med. Chem. 2021, 64, 9677-9710.
Grants:
- NCN – Preludium Bis, 2021-2025: Application of PROTAC strategy for controlling Rab geranylgeranyl transferase and Rab proteins;
- NCN – Sonata Bis, 2015-2021: Design and synthesis of probes for RabGGTase profiling and their application for identification of the site of phosphonocarboxylate inhibitors's interaction with the enzyme and potential off-targets;
- NCN – Preludium, 2017-2020: Synthesis of 2-phosphonocarboxylates as potential covalent inhibitors of Rab geranylgeranyl transferase;
- * NCN – Opus, 2019-2021: Unravelling the controversial role of palmitoleic acid in the dietary prophylaxis of carbohydrate and lipid homeostasis disorders *Prof. Błażewska group plays a role of investigator in this project.
Keywords:
α-phosphonocarboxylates, α-phosphonocarboxylic acids, Rab GTPases, Rab geranylgeranyl transferase (RGGT), Parkinson’s disease, inhibitors
List of internship proposal in this research team:
Design and synthesis of linkers connecting two biologically active warheads. Synthesis of peptides as selective inhibitors of protein-protein interactions.
The portfolio of research groups was created as part of the Programme "STER" – Internationalisation of doctoral schools” as part of the realization of the project “Curriculum for advanced doctoral education & taining – CADET Academy of Lodz University of Technology”.
Institute of Organic Chemistry I-32
Head of the unit:
Prof. Łukasz Albrecht, PhD, DSc
Potential promoters:
Prof. Łukasz Albrecht, PhD, DSc
Contact person:
Prof. Łukasz Albrecht, PhD, DSc, phone: 42-631-31-57, lukasz.albrecht@p.lodz.pl
Scope of activities:
The main scientific topics realized in our group include:
- development of new methods of asymmetric synthesis, with particular emphasis on organocatalysis,
- design of novel reactivities providing access to relevant building blocks
- utilization of photocatalysis in organic synthesis
- studies on the reaction mechanisms with application of modern analytical methods
- application of NMR targeted and untargeted methodologies for food authentication and detection of counterfeit products
- metabolic profiling of biological samples by means of NMR spectroscopy
Present activities:
- Studies on the dearomative organocatalytic approaches providing functionalization of aromatic systems
- Design of the new organocatalytic higher-order cycloadditions, paving way for the better understanding of those processes
- Utilization of N-heterocyclic carbene catalysis in dearomative reactions
- Development of new methods for the activation of organic compounds
- Analysis of the metabolic profile of varietal honeys by NMR
- Application of 1H NMR spectroscopy for the assessment of the authenticity of perfumes
- Metabolic profiling of gestational diabetes in women during pregnancy
- Investigation of the qualitative and quantitative composition of selected species of pepper and their biological properties
Future activities:
Development of NMR methods for overcoming modern civilization problems related to health as well as food and drugs fraud.
Publications/patents, awards, projects Publications:
- Przydacz, A.; Skrzynska, A.; Albrecht, ́Ł. Breaking Aromaticity with Aminocatalysis: A Convenient Strategy for Asymmetric Synthesis. Angew. Chem., Int. Ed. 2019, 58, 63−73.
- Skrzynska, A.; Frankowski, S.; Topolska, A.; Dyguda, M.; Gao, X.-Y.; Xu, C. J.; Chen, Y.-C.; Albrecht, Ł. Enantioselective H-bond-directed vinylogous iminium ion strategy for the functionalization of vinyl-substituted heteroaryl aldehydes. Chem. Commun. 2021, 57, 1667−1670.
- Romaniszyn, M.; Gronowska, K.; Albrecht, Ł. Remote Functionalization of 4-(Alk-1-en-1-yl)-3-Cyanocoumarins via the Asymmetric Organocatalytic 1,6-Addition, Adv. Synth. Catal. 2021, 22, 5116-5121.
- Pacholczyk-Sienicka, B.; Ciepielowski, G.; Albrecht, Ł. The application of NMR spectroscopy and chemometrics in authentication of spices. Molecules 2021, 26, 382.
Research projects:
- “Game of electrons: new organocatalytic higher-order cycloadditions in organic synthesis” OPUS 21 from the National Science Centre, Poland.
- “Lewis Base Catalyzed Asymmetric Reactions of Aromatic Carbonyl Substrates” Sheng programme (Grant No. UMO-2018/30/Q/ST5/00466) from the National Science Centre, Poland.
Keywords:
catalysis, chirality, asymmetric organocatalysis, cycloadditon reactions, organic synthesis, photocatalysis, products authentication by NMR, metabolic profiling
List of internship proposal in this research team:
Postdoctoral and doctoral fellowships related to scientific topics stated above are available in the group.
The portfolio of research groups was created as part of the Programme "STER" – Internationalisation of doctoral schools” as part of the realization of the project “Curriculum for advanced doctoral education & taining – CADET Academy of Lodz University of Technology”.
Institute of Organic Chemistry I-32
Head of the unit:
Prof. Tomasz Janecki PhD, DSc
Contact person:
Prof. Tomasz Janecki PhD, DSc, phone: 48-42-631-32-20, tomasz.janecki@p.lodz.pl
Scope of activities:
The main area of interest is stereoselective synthesis of organic compounds (including organophosphorus compounds) with potential cytotoxic activity and search for the structure-activity relationship (SAR). Our synthetic targets are usually compounds containing 2-alkylidene-1-oxoheterocyclic skeleton which are structurally related to a big group of natural a-alkylidene g- or dlactones or lactams with well-recognized cytotoxic activity. In our research we often use, developed in our laboratory, Horner-Wadsworth-Emmons methodology for the introducing of alkylidene moiety onto the heterocyclic ring in regioselective manner. We also developed enantioselective synthesis of the target compounds by using phosphoryl groups containing menthyl or 1-phenylethylamino residues as chiral auxiliaries. Obtained compounds are tested for their biological activity and in particular cytotoxic activity, in cooperation with Medical University of Lodz.
Present activities:
Currently we realize stereoselective synthesis of three libraries of 2- alkylidene-1-oxoheterocycles, with very promising cytotoxic activity. These are variously alkyl or aryl substituted 3-methylidenetetrahydropyran-4-ones, 3-methylidene-1-tosyl-2,3-dihydroquinolin-4(1H)-ones and 3-methylidene-1- tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones. In the final stage of the synthesis we utilize appropriate organophosphorus reagent for the HornerWadsworth-Emmons olefination of formaldehyde.
We also perform the synthesis of substituted in position 2, regioisomeric N,Oanti and N,O-syn 3-diethoxyphosphorylfuroquinoline-4,9-diones, which posses vey high cytotoxic activity. One of the obtained compounds with highest cytotoxic activity is being currently tested to established its mode of action.
Future activities:
Enancjoselective synthesis of 3-methylidenetetrahydropyran-4-ones, 3-methylidene-1-tosyl-2,3- dihydroquinolin-4(1H)-ones and 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones using dimenthoxyphosphoryl group as chiral auxiliary.
Publications/patents, awards, projects:
- Kędzia Jacek, Bartosik Tomasz, Drogosz Joanna, Janecka Anna, Krajewska Urszula, Janecki Tomasz „Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones” Molecules 2019, 24, 1868/1- 1868/14.
- Bartosik Tomasz, Kędzia Jacek, Drogosz-Stachowicz Joanna, Janecka Anna, Krajewska Urszula, Mirowski Marek, Janecki Tomasz, „Synthesis of 2,2,6-Trisubstituted 5-Methylidenetetrahydropyran4-ones with Anticancer Activity” Molecules 2020, 25, 611
- Jakub Modranka, Joanna Drogosz-Stachowicz, Anna Pietrzak, Anna Janecka, Tomasz Janecki, “Synthesis and structure-activity relationship study of novel 3- diethoxyphosphorylfuroquinoline4,9-diones with potent antitumor efficacy”, European Journal of Medicinal Chemistry 2021, 219, 113429.
- Tomasz Janecki, “Stereoselective Synthesis of Methylidenecoumarins and Methylideneuracils as Novel, Potent Anticancer Agents” The 17-th Annual Congress of International Drug Discovery Science & Technology, July 25-27, 2019, Kyoto, Japan, Lecture
Keywords:
organic synthesis, 2-alkylidene-1-oxoheterocycles, organophosphorus compounds, Horner-WadsworthEmmons reaction, cytotoxic activity, structure activity relationship
The portfolio of research groups was created as part of the Programme "STER" – Internationalisation of doctoral schools” as part of the realization of the project “Curriculum for advanced doctoral education & taining – CADET Academy of Lodz University of Technology”.