Ruthenium Complex Bearing a Hydroxy Group Functionalised N-Heterocyclic Carbene Ligand – A Universal Platform for Synthesis of Tagged and Immobilised Catalysts for Olefin Metathesis

Six olefin metathesis catalysts, based on a common ruthenium precursor featuring a hydroxy-substituted N-heterocyclic carbene ligand, were successfully prepared and fully characterised. As proof-of-concept, two of them ([Ru]isonico and [Ru]dmab) were directly immobilised on a solid support. These non-covalently heterogenised catalysts are efficient in different metathesis reactions and sufficiently stable to be used for repeated runs under batch and continuous flow conditions. In nonpolar media such as n-hexane, the catalytic character of the metathesis reactions is truly heterogeneous, and the contamination of the products with ruthenium is very low. © 2021 The Authors. European Journal of Organic Chemistry published by Wiley-VCH Gmb

Dendritic glycopolymers based on dendritic polyamine scaffolds: view on their synthetic approaches, characteristics and potential for biomedical applications

In this review we highlight the potential for biomedical applications of dendritic glycopolymers based on polyamine scaffolds. The complex interplay of the molecular characteristics of the dendritic architectures and their specific interactions with various (bio)molecules are elucidated with various examples. A special role of the individual sugar units attached to the dendritic scaffolds and their density is identified, which govern ionic and H-bond interactions, and biological targeting, but to a large extent are also responsible for the significantly reduced toxicity of the dendritic glycopolymers compared to their polyamine scaffolds. Thus, the application of dendritic glycopolymers in drug delivery systems for gene transfection but also as therapeutics in neurodegenerative diseases has great promisePublikacja w ramach programu Royal Society of Chemistry "Gold for Gold" 2014 finansowanego przez Uniwersytet Łódzk

Plasmodium falciparum proteinases: cloning of the putative gene coding for the merozoite proteinase for erythrocyte invasion (MPEI) and determination of hydrolysis sites of spectrin by Pf37 proteinase

Numerous proteinase activities have been shown to be essential for the survival of Plasmodium falciparum. One approach to antimalarial chemotherapy, would be to block specifically one or several of these activities, by using compounds structurally analogous to the substrates of these proteinases. Such a strategy requires a detailed knowledge of the active site of the proteinase, in order to identify the best substrate for the proteinase. Aiming at developing such a strategy, two proteinases previously identified in our laboratory, were chosen for further characterization of their molecular structure and properties: the merozoite proteinase for erythrocytic invasion (MPEI), involved in the erythrocyte invasion by the merozoites, and the Pf37 proteinase, which hydrolyses human spectrin in vitro

Uso potencial de ciertas lectinas para el seguimiento del estado de salud de pacientes operados de cáncer colorrectal

The reactivity of 15 lectins or their derivatives (commercially available) were determined in blood serum of a control group of 13 apparently healthy humans in comparison with: (I) a group of 28 patients of colorectal cancer, explored 1 day before surgical exeresis; (II) another group of 15 subjects analysed 4-7 days after surgery; and (III) 27 subjects investigated 7-9 months after their operation. The lectins or their derivatives were selected taking into consideration the peculiarities of their specificities for the glycoconjugate ligands in the sera. A very different reactivity was found. Results pointed to certain variability for the pathological sera analysed. In addition, differences in the lectin reactivity depending on the time of surgical exeresis (4-7 days in comparison to 7-9 months) were detected. The usefulness of the assays with certain lectins (SNA = Sambucus nigra, LEL = Licopersicon esculentum and LTL = Lotus tetragonolobus) in the follow-up of the health status of patients operated for colorectal cancer is discussed.Se ha determinado la especificidad de la reacción de 15 lectinas o sus derivados (disponibles comercialmente) con glicoconjugados de sueros sanguíneos de un grupo control de 13 humanos aparentemente sanos, en comparación con: (I) un grupo de 28 pacientes de cáncer colorrectal, explorados 1 día antes de la intervención quirúrgica; (II) otro grupo de 15 sujetos analizados 4-7 días después de dicha intervención; y (III) con 27 sujetos investigados 7-9 meses después de la operación (en estado satisfactorio de salud). Las lectinas o sus derivados fueron seleccionados tomando en consideración las peculiaridades de sus respectivas especificidades en relación con los ligandos de naturaleza glicoconjugada de los sueros analizados. Se halló reactividad diferente según los sueros. Así, se detectaron diferencias en la intensidad de la reacción, dependiendo del tiempo transcurrido desde la intervención quirúrgica (4-7 días en comparación con 7-9 meses). Por último, se discute la utilidad de las determinaciones con ciertas lectinas (las de SNA = Sambucus nigra, LEL = Licopersicon esculentum y LTL = Lotus tetragonolobus) en el seguimiento del estado de salud de personas operadas de cáncer colorrectal, como valoraciones complementarias de las habituales empleadas con esta finalidad

Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as Carriers of DNA and RNA

We have evaluated the potential use of various polyamidoamine (PAMAM) dendrimer [dendrimer, generation (G) 2-4] conjugates with cyclodextrins (CyDs) as novel DNA and RNA carriers. Among the various dendrimer conjugates with CyDs, the dendrimer (G3) conjugate with α-CyD having an average degree of substitution (DS) of 2.4 [α-CDE (G3, DS2)] displayed remarkable properties as DNA, shRNA and siRNA delivery carriers through the sensor function of α-CDEs toward nucleic acid drugs, cell surface and endosomal membranes. In an attempt to develop cell-specific gene transfer carriers, we prepared sugar-appended α-CDEs. Of the various sugar-appended α-CDEs prepared, galactose- or mannose-appended α-CDEs provided superior gene transfer activity to α-CDE in various cells, but not cell-specific gene delivery ability. However, lactose-appended α-CDE [Lac-α-CDE (G2)] was found to possess asialoglycoprotein receptor (AgpR)-mediated hepatocyte-selective gene transfer activity, both in vitro and in vivo. Most recently, we prepared folate-poly(ethylene glycol)-appended α-CDE [Fol-PαC (G3)] and revealed that Fol-PαC (G3) imparted folate receptor (FR)-mediated cancer cell-selective gene transfer activity. Consequently, α-CDEs bearing integrated, multifunctional molecules may possess the potential to be novel carriers for DNA, shRNA and siRNA

Neoglycoproteins as carbohydrate antigens : synthesis, analysis, and polyclonal antibody response

The analysis and polyclonal antibody response for newly synthesized maltose-BSA conjugate neoglycoproteins is described. In this first proof of concept study, a simple carbohydrate antigen, maltose, was linked to BSA by reductive amination. An aglycone spacer was utilized to conserve the intact annular maltose structure and to promote the accessibility of the carbohydrate immunogen hapten during immunization. The neoglycoproteins were investigated by CGE and the number of conjugated maltose residues was determined by MALDI-TOF MS. The neoglycoproteins were then evaluated by immunization of BALB/c mice and the polyclonal antibody response was tested by ELISA as evidence for the presence of sugar-containing epitope-specific antibodies. Selective antibody binding was demonstrated to the synthesized neoglycoproteins with different (low and high) glycosylation degrees suggesting the possible use of this approach to generate antibodies. Moreover, the polyclonal antibody response was not inhibited by maltose or other simple carbohydrates to confirm presence of the neoglycoprotein-specific antibodies