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

Wstępne próby konstrukcji bibliotek peptydowych jako narzędzia w diagnostyce nowotworów złośliwych tarczycy

Introduction: Cancer of thyroid gland is the most common malignancy of the endocrine system. The treatment improvement could be achieved by early diagnosis. The aim of the study was to identify cancer specific antigenes with use of peptide libraries. Material and methods: The material from 6 patients with thyroid cancer (4 with papillary cancer, 1 with follicular cancer and 1 with oxyphilic tumor) were analyzed. It was performed with use of lipophylic peptide libraries by direct comparison of staining of specimens prepared from normal and malignant tissue. Results: Preliminary results confirm practical value of peptide libraries in early diagnostics of thyroid cancer. Conclusions: It is important to optimize construction of peptide libraries by using different staining agents hydrolyzed by proteases.Wstęp: Nowotwory złośliwe tarczycy należą do najczęstszych nowotworów złośliwych układu endokrynnego. Poprawa wyników leczenia wiąże się z postępem wczesnej diagnostyki raka. Celem niniejszych badań jest poszukiwanie wskaźników nowotworowych za pomocą bibliotek peptydowych umieszczonych na podłożu z bibuły. Materiał i metody: Analizie poddano tkanki pobrane od 6 pacjentów: 4 z rakiem brodawkowatym tarczycy, 1 z nowotworem pęcherzykowym oraz 1 pacjenta z rakiem oksyfilnym. Badania wykonywano z wykorzystaniem bibliotek peptydowych lipofilowych, porównując tkankę zdrową i chorą oraz oceniając zmianę zabarwienia w poszczególnych bibliotekach. Wyniki: Wstępne wyniki wskazują, że biblioteki peptydowe można zastosować w diagnostyce nowotworów tarczycy. Wnioski: Niezbędna jest optymalizacja budowy bibliotek peptydowych, gdzie konieczne jest zastosowanie innego barwnika hydrolizowanego przez proteazy

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

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