Modulating the Physicochemical Properties of Chitin and Chitosan as a Method of Obtaining New Biological Properties of Biodegradable Materials

Physical and chemical modifications of chitin and chitosan allow for obtaining new functional properties of the natural polymers. This is a particularly valuable feature for the design and manufacture of new materials for medical applications. Due to their wide and varied biological activity, chitin and chitosan materials are increasingly used as dressing materials with antibacterial and hemostatic properties and as materials accelerating the regeneration of damaged tissues because of stimulation of granulation tissue formation, re-epithelialization and reduction of the formation of scar tissue. In addition, chitosan derivatives have antifungal, antiviral, anticancer activity. The increasing use of chitin and chitosan also has a positive impact on the environment, as it is obtained as a result of chitin deacetylation, usually isolated from shellfish shells. The main source of chitin is waste coating of crustaceans. The annual natural reproducibility of chitin by biosynthesis is estimated at 2–3 billion tons. Our interest in the use of biodegradable biopolymers derived from chitin concerns the design, synthesis in laboratory scale, testing new material properties and the final implementation of new developments for industrial practice of new dressing materials useful in the treatment of bleeding wounds (haemostatic properties) as well as in the regeneration of wounds and ulcers of various etiologies. Examples of chitin-based dressing materials introduced by Tricomed SA are Medisorb R Ag, Medisorb R Membrane, Medisorb R Powder and Tromboguard®

Towards intelligent drug design system: Application of artificial dipeptide receptor library in QSAR-oriented studies

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 m-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.NC

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

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-dPhedPhe-OH, H-dCysdPhedPhe-OH, H-CysTyrTyr-OH, H-dPhedPhedCys-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

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

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 (Et3N, 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 E. coli and S. aureus bacterial strains, where the most active was ITC 9e

The use of chitin and chitosan in manufacturing dressing materials

Despite continuous progress in the development of advanced dressing materials, there is a constant need for dressings used in an environment of infected and hard-to-heal wounds. Dressings that meet the above described requirements are products based on chitin and its derivatives. Chitosan and chitin derivative dressings are now becoming a very effective medical device in healing hard-to-heal wounds, as well as in the control of severely bleeding wounds. Chitosan and chitin are particularly valuable raw materials that accelerate wound healing processes, and they are also biocompatible and antibacterial. Dressings made of butyric-acetic chitin copolyester are intended for treating wounds of various aetiologies, including chronic wounds in which the healing process is disturbed by concomitant diseases. Materials based on chitosan are also widely used in the area of heavily bleeding and chronic wounds

Novel side reactions accompanying activation and aminolysis of N-benzoyl-2-alkylserines.

2-Phenyl-4-alkyl-4-hydroxymethyl-1,3-oxazolones (2a-d) have been identified as side products accompanying activation of N-benzoyl-2-alkylserines (1a-d). Oxazolones 2a-d in the presence of amine rearrange subsequently to corresponding 4-alkyl-2-phenyl-4,5-dihydro-1,3-oxazole-5 carboxylic acids (4a-d) at a 20-68% yield

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

A series of new analogs of nitrogen mustards (4a–4h) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and β-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 A and 4a, with an inhibitory concentration of AChE IC50 = 0.051 µM; 0.055 µM and BACE1 IC50 = 9.00 µM; 11.09 µM, respectively

1,3-OXAZOLIDIN-5-ONES DERIVED FROM PROLINE AS CHIRAL COMPONENTS IN THE SYNTHESIS OF PREDICTIVE ENANTIOSELECTIVE COUPLING REAGENTS

1,3-Oxazolidin-5-ones derived from both enantiomers of proline and trichloroacetaldehyde were prepared and applied as amine component in the synthesis of chiral predictive triazine based coupling reagents. The usefulness of these reagents in the condensations yielding enantiomerically enriched products from racemic substrates was presented

Synthetic extracellular matrix as a substrate for regenerative medicine

The work presents materials characteristics of fibrous polysaccharide substrates (calcium alginate, CA) modified with short peptides. Three types of synthesized peptides (hexapeptides) were composed of: cysteine (C) and tryptophan (W) named - (WWC)2or cysteine (C) and tyrosine (Y) named (YYC)2 or phenyloalanine (F) named 6F. The peptides size distribution (DLS method) showed that they agglomerated in an alcohol medium. These results were used to select a modification method of the fibrous substrates i.e. the peptides were deposited on the fibrous alginate substrate by the electrospraying technique. Using this method three kinds of polysaccharide- peptides systems were obtained i.e.: CA/(WWC)2, CA/(YYC)2CA/6F. As a reference material, the pure calcium alginate fibrous substrate was used. The results of modification with short peptides were evaluated via scanning electron microscopy (SEM): small aggregates were observed (40-100 nm) on the surface of fibers, and the fibers size remained the same after modification (11-12 μm). The size of aggregates depended on the kind of short peptide; the smaller (40 nm) aggregates were observed when the peptide had only aromatic chain (6F), the bigger (<100 nm) ones were observed when the peptide had heterocyclic rings in the chain (WWC and YYC). All materials were contacted with osteoblast-like cells (MG-63) to test biocompatibility (cells viability after 3 and 7 days) and the results proved showed higher viability in the polysaccharide-peptide system which increased with the time of observation. The durability of polysaccharide-peptide systems was tested using the enzymatic assay: collagenase confirmed the stability of materials. The progress of degradation rate was observed using infrared spectroscopy (FTIR-ATR) - the ratio on bands with C-O and C-OH increased after degradation under in vitro conditions.Results of the investigations on the fibrous substrates have confirmed that the system is a good model of an extracellular matrix (ECM) due to its chemical composition and microstructure which both have biomimetic characteristics. Thus, it may be used as a filling of bone defects supporting the regeneration of the damaged tissue. Additionally, it may also serve as the model research system of ECM