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A new crystalline complex of dl -serine and squaric acid (H 2 Sq) in stoichiometric ratio 1:1 ( dl -Ser·HSq) was synthesized, isolated and structurally characterized by single crystal X-ray diffraction. The compound crystallizes in the monoclinic space group P2 1 /n and its structure consists of a 3D supramolecular network of hydrogensquarate anions and serinium cations directed by intermolecular hydrogen bonding interactions. The 3D network is formed by hydrogen bonds with participation of C O–OH, hydrogensquarate ion and NH 3 + group, (Sq) C O…O C (OH) (2.525 Å), – NH 3 + …O C (Sq) (2.915, 2.985 and 3.016 Å), hydroxyl group CH 2 –OH…O C (Sq) (2.739 Å), O…H–N + (3.016 Å) and (C–OH A …O C (Sq) (3.242), respectively. The structural information shows a new structural motif, a non-classic α-chain of the hydrogensquarate anions with dihedral angle between neighbouring HSq − anions 43.66°. The Raman and infrared spectra of the new crystal were measured in the 4000–50 cm −1 and 4000–400 cm −1 region frequency range respectively. The assignment of bands in infrared and Raman spectra of the crystal was performed on the basis of DFT (B3LYP) calculations, X-ray structural results and by the comparison with literature data. [ABSTRACT FROM AUTHOR]

Review: 10 refs. [ABSTRACT FROM AUTHOR]

Leu-Arg is a kyotorphin receptor antagonist. It is very important to control antinociception and this could be achieved by modifications in agonist's or antagonist's molecules. Two analogues of Leu-Arg were synthesized, their IR- spectral characteristics were defined, and preliminary docking studies were performed. The results show that new analogues bind receptor thus they could be used for further analysis and their biological activity could be tested in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Arginine residues are very important for the structure of proteins and their action. Arginine is essential for many natural processes because it has unique ionizable group under physiological conditions. Numerous mimetics of arginine were synthesized and their biological effects were evaluated, but the mechanisms of actions are still unknown. The aim of this study is to see if oxy- and sulfoanalogues of arginine can be recognized by human arginyl-tRNA synthetase (HArgS) -- an enzyme responsible for coupling of L-arginine with its cognate tRNA in a two-step catalytic reaction. We make use of modeling and docking studies of adenylate kinase (ADK) to reveal the effects produced by the incorporation of the arginine mimetics on the structure of ADK and its action. Three analogues of arginine, L-canavanine (Cav), L-norcanavanine (NCav), and L-sulfoarginine (sArg), can be recognized as substrates of HArgS when incorporated in different peptide and protein sequences instead of L-arginine. Mutation in the enzyme active center by arginine mimetics leads to conformational changes, which produce a decrease the rate of the enzyme catalyzed reaction and even a loss of enzymatic action. All these observations could explain the long-lasting nature of the effects of the arginine analogues. [ABSTRACT FROM AUTHOR]

This paper deals with the chiral separation of Fmoc- and Z-derivatives of natural and unnatural sulfur containing amino acids by micro-HPLC. The separations were carried out in microbore columns packed with a new material based on Ristocetin A bonded to 3.5 μm silica gel. The columns were run in the normal phase, polar organic mode as well as in the reversed phase mode, whereby best results were obtained with the reversed-phase mode using mixtures of triethylamine acetate (TEAA) buffer and methanol as mobile phases. [Copyright &y& Elsevier]

Aroyl hydrazones have been intensively investigated over the last decades due to their various biological properties such as anticancer, antibacterial and antimicrobial effects. Herein, we examine the anti-proliferative effect of two new aroyl hydrazones used in a combination with AVPI- and RGD -- peptides. The anti-proliferative activity is checked by MTT assay after 72h of treatment on MDA-MB-231 breast cancer cells. Though the aroyl hydrazone derivatives used as single agents shows a high activity, the combination is found not beneficial. [ABSTRACT FROM AUTHOR]

One of the potent somatostatin analogs, BIM-23052 (DC-23-99) d-Phe-Phe-Phe-d-Trp-Lys-Thr-Phe-Thr-NH2, has established in vitro growth hormone inhibitory activity in nM concentrations. It is also characterized by high affinity to some somatostatin receptors which are largely distributed in the cell membranes of many tumor cells. Herein, we report the synthesis of a series of analogs of BIM-23052 containing halogenated Phe residues using standard solid-phase peptide method Fmoc/OtBu-strategy. The cytotoxic effects of the compounds were tested in vitro against two human tumor cell lines—breast cancer cell line and hepatocellular cancer cell line, as well as on human non-tumorigenic epithelial cell line. Analogs containing fluoro-phenylalanines are cytotoxic in μM range, as the analog containing Phe (2-F) showed better selectivity against human hepatocellular cancer cell line. The presented study also reveals that accumulation of halogenated Phe residues does not increase the cytotoxicity according to tested cell lines. The calculated selective index reveals different mechanisms of antitumor activity of the parent compound BIM-23052 and target halogenated analogs for examined breast tumor cell lines. All peptides tested have high antitumor activity against the HepG2 cell line (IC50 ≈ 100 μM and SI > 5) compared to breast cells. This is probably due to the high permeability of the cell membrane and the higher metabolic activity of hepatocytes. In silico docking studies confirmed that all obtained analogs bind well with the somatostatin receptors with preference to ssrt3 and ssrt5. All target compounds showed high hydrolytic stability at acid and neutral pH, which mimic physiological condition in stomach and human plasma. [ABSTRACT FROM AUTHOR]

AVPI-(Ala-Val-Pro-Ile) and RGD-(Arg-Gly-Asp) peptides have recently attracted a growing interest in the anticancer drug design and development. Following the concept of combining two fragments with different functionalities in order to achieve increased effects, we present herein the synthesis of two AVPI-RGD peptides. The impact of the performed chemical modifications on the anti-proliferative activity of these peptides was evaluated at MDA-MB-231 cancer cells. It was found that the conjugated peptide with modifications at proline and arginine residues showed a higher anti-proliferative effect than the parent AVPI-RGD molecule. Furthermore, it was observed that the effect of AVHypI-AgbGD vs. that of its co-administrated structural subunits was higher. The results obtained in this work suggested that the introduced substitutions and the conjugation of the two functional motifs benefit the anti-proliferative activity of the parent peptides. [ABSTRACT FROM AUTHOR]

Peptides have been developed during the last decade as an alternative for delivery and targeting of drugs, and for the visualization of tumors. In contrast to the antibodies, the peptides are smaller and can be delivered to the cytoplasm by various mechanisms. RGD peptides have been developed as potent integrin ligands and antagonists that inhibit the adhesion and formation of tumor metastases or directly induce apoptosis by activating caspases. A series of short RGD mimetics and their conjugates are synthesized and their cytotoxic activity against four cancer cell lines is examined. RGD peptides modified by shorter homologues of with arginine (α-amino-4-guanidinobutyric acid (Agb) and α-amino-3-guanidino-propionic acid (Agp)) show an increase of the cytotoxic effect compared to that of the parent RGD peptide. [ABSTRACT FROM AUTHOR]

Hydrazones have versatile properties that make them promising for a range of possible applications. In this study, we examined a library of 17 aroylhydrazones derived from nicotinic acid hydrazide (1-12) and isonicotinic acid hydrazide (A-E) created by us for their biological activity. The antiproliferative activity of the compounds was investigated on non-tumour MCF-10A cells and cancer cell lines, MCF-7 and MDA-MB-231. Four compounds were selected as most active in cell growth inhibition of the tumour cell lines. These compounds, 5, 11, C and E, were tested on four additional cell lines: non-tumour BJ and cancer cell lines, HeLa, HepG2 and HT-29. Compounds 5 and E exhibited the highest selectivity index on cancer cell lines MDA-MB-231, HeLa and HepG2. High selectivity to MCF-7 cells was demonstrated with compound 5. Compound C was very selective to HepG2 cells as well as to MDA-MB-231 but to a lesser degree. Compound 11 showed selectivity against MDA-MB-231. The obtained results allow assessing the structure–activity relationship of the compounds and provide insight into the further development of this group of aroylhydrazones as more potent and selective anti-neoplastic agents. [ABSTRACT FROM AUTHOR]

Myosmine, 3-(1-pyrroline-2-yl) pyridine is a minor tobacco alkaloid that has also been found in various widely used foods. Recently, this phytochemical has been gaining an increasing interest as a potential risk factor for the development of oesophageal adenocarcinoma. This study aimed to examine the effects of myosmine on the cell viability and proliferative activity of erythroleukemia and hepatocellular carcinoma cells and to obtain additional information about the mechanisms underlying its cytotoxic activity. The in vitro cytotoxic effect of myosmine on the HepG2 and MEL tumour cell lines was assessed by MTT dye reduction and trypan blue dye exclusion assays. The alterations in the tumour cell morphology induced by myosmine were analysed by fluorescent microscopy after staining with acridine orange (AO)/ethidium bromide (EtBr) and 4′,6-diamidine-2′-phenylindole dihydrochloride (DAPI). Annexin V-FITC/propidium iodide (PI) staining was used to assess the apoptosis-inducing ability of myosmine. The modulating action of antioxidant treatment on myosmine-induced cytotoxicity against the HepG2 tumour cell line was also examined. The cell viability tests indicated that myosmine induced a significant dose-dependent reduction of the viability and proliferative activity of both tumour cell lines. Fluorescent microscopy studies revealed marked alterations in the morphology of myosmine-treated tumour cells with signs of cell cycle arrest and apoptosis. The results of the simultaneous treatment with myosmine and vitamin C showed modulating activity of vitamin C on the cytotoxic effect of myosmine with concentration- and time-dependent variations. The presented results could contribute to the assessment of the potential health risks associated with the dietary myosmine exposure. Abbreviations AO: acridine orange; DAPI: 4',6-diamidine-2'-phenylindole dihydrochloride; DMEM: Dulbecco's modified Eagle medium; DMSO: dimethyl sulfoxide; EtBr: ethidium bromide; FITC: fluorescein isothiocyanate; GERD: gastroesophageal reflux disease; MEL: murine erythroleukemia; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NNN: N'-nitrosonornicotine; PBS: phosphate buffered saline; PI: propidium iodide [ABSTRACT FROM AUTHOR]

Highlights: [•] Separation of unusual AAs enantiomers was performed in HPLC. [•] Teicoplanin or polysaccharide based chiral stationary phases were employed. [•] Non-blocked AAs enantiomers were best separated on teicoplanin based columns. [•] Blocked AAs enantiomers were best resolved on Chirobiotic T or Chiralpak IC columns. [•] Chiral selector structure affected elution order of enantiomers. [ABSTRACT FROM AUTHOR]

A novel methodology for the synthesis of sulfo- and oxy-modified amino acid analogues of arginine (Arg) has been developed using both conventional and polymer assisted synthesis from ready available amino acid precursor. Introduction of guanidine group was made also by the MWA synthesis. The in vitro inhibitory effect of the amino acid analogues on the growth of murine erythroleukemia cells, clone F4N in culture was also studied. [ABSTRACT FROM AUTHOR]

To elucidate the structural features determining δ-opioid receptor properties of enkephalin analogues containing Cys(O2NH2) in position 2, a series of Cys2-containing derivatives were synthesized and tested for their effectiveness in depressing electrically evoked contractions of the mouse vas deferens (predominantly enkephalin-selective δ-opioid receptors) and the guinea-pig ileum (μ- and κ-opioid receptors). The peptidase resistance of the compounds was also tested. The ratio IC50 in the guinea-pig ileum/IC50 in the mouse vas deferens, indicating selectivity for δ-opioid receptors, was high for Cys(O2NH2)2-containing analogues and especially for [Cys(O2NH2)2, Leu5]enkephalin, which was about seven times more selective than δ-opioid receptor selective ligand cyclic [d-Pen2, d-Pen5]enkephalin (DPDPE). The dissociation constant (KA) and relative efficacy (erel) of the compounds in the mouse-isolated vas deferens were determined using explicit formulae derived by fitting of the data points with two-parametric hyperbolic function. The obtained values for KA and erel suggest that: (i) incorporation of Cys(O2NH2)2 in the molecule of [Leu5]enkephalin highly increases the efficacy and does not change significantly the affinity of the respective analogues to δ-opioid receptors; [Cys(O2NH2)2, Leu5]enkephalin has higher affinity than DPDPE, but is less resistant to enzyme degradation; the effect of this modification on the efficacy is decreased when methionine is in position 5; (ii) d-configuration of Cys(O2NH2)2-containing analogues increases their peptidase resistance, but reduces efficacy and affinity of the peptides towards δ-opioid receptors; (iii) the substitution of Cys(O2NH2) with Hcy(O2NH2) reduces the efficacy, affinity and potency of the respective analogues and maintains their sensitivity to endogenous peptidases; (iv) the substitution of the sulfonamide group with benzyl group in the molecule of Cys in position 2 decreases their efficacy and affinity toward δ-opioid receptors, but attaches resistance to enzyme degradation. The results obtained in this study allow: (i) to involve the receptor affinity and agonist efficacy as drug-design consideration for δ-opioid receptor properties of newly synthesized compounds and (ii) to characterize some of the structural features, which set the pattern for their opioid profiles. [Copyright &y& Elsevier]

Methionine aminopeptidase, known to be encoded by single genes in prokaryotes, is a cobalt-dependent enzyme that catalyzes the removal of N-terminal methionine residues from nascent polypeptides. Three ORFs encoding putative methionine aminopeptidases from the genome of cyanobacterium Synechocystis sp. strain PCC6803, designated as slr0786 (map-1), slr0918 (map-2) and sll0555 (map-3) were cloned and expressed in Escherichia coli. The purified recombinant proteins encoded by map-1 and map-3 had much higher methionine aminopeptidase activity than the recombinant protein encoded by map-2. Comparative analysis revealed that the three recombinant enzymes differed in their substrate specificity, divalent ion requirement, pH, and temperature optima. The broad activities of the iso-enzymes are discussed in light of the structural similarities with other peptidase families and their levels of specificity in the cell. Potential application of cyanobacterial MetAPs in the production of recombinant proteins used in medicine is proposed. This is the first report of a prokaryote harboring multiple methionine aminopeptidases. [ABSTRACT FROM AUTHOR]