Conjugates of adenosine mimetics and arginine-rich peptides serve as inhibitors and fluorescent probes but not as long-lifetime photoluminescent probes for protein arginine methyltransferases.

The conjugates of an adenosine mimetic and oligo-l-arginine or oligo-d-arginine (ARCs) were initially designed in our research group as inhibitors and photoluminescent probes targeting basophilic protein kinases. Here, we explored a panel of ARCs and their fluorescent derivatives in biochemical assays with members of the protein arginine methyltransferase (PRMT) family, focusing specifically on PRMT1. In the binding/displacement assay with detection of fluorescence anisotropy, we found that ARCs and arginine-rich peptides could serve as high-affinity ligands for PRMT1, whereas the equilibrium dissociation constant values depended dramatically on the number of arginine residues within the compounds.

Macrocyclic open-chain carbazole receptors for carboxylate binding.

The anion recognition properties of six synthetic acyclic and macrocyclic carbazole-based receptors have been studied by H-NMR as well as with COSMO-RS calculations towards acetate, benzoate, lactate, sorbate and formate. The receptors differed by the number and geometry of hydrogen-bond donor (HBD) sites, the nature and length of the linker(s) between the HBD sites and the cyclic or non-cyclic nature. The binding ability of the receptors is strongly influenced by the structure and steric variables of the receptors and anions.

LogP determination for highly lipophilic hydrogen-bonding anion receptor molecules.

Lipophilicity, usually expressed as octanol-water partition coefficient (logP), is an important property in biomedical research, drug design and technology. However, high logP values of complex hydrogen-bonding molecules are not easy to measure or calculate. Exemplary problematic molecules are prospective active components (ionophores) of polymeric sensor membranes - the working elements of ion-selective electrodes.

Design, synthesis and application of carbazole macrocycles in anion sensors.

Carboxylate sensing solid-contact ion-selective electrodes (ISEs) were created to provide a proof-of-concept ISE development process covering all aspects from in silico ionophore design to functional sensor characterization. The biscarbazolylurea moiety was used to synthesize methylene-bridged macrocycles of different ring size aiming to fine tune selectivity towards different carboxylates. Cyclization was achieved with two separate strategies, using either amide synthesis to access up to -[CH]- macrocycles or acyl halides to access up to -[CH]- macrocycles.

A Selective Biligand Inhibitor of CK2 Increases Caspase-3 Activity in Cancer Cells and Inhibits Platelet Aggregation.

Cancer cells express high levels of CK2, and its inhibition leads to apoptosis. CK2 has therefore emerged as a new drug target for cancer therapy. A biligand inhibitor ARC-772 was constructed by conjugating 4-(2-amino-1,3-thiazol-5-yl)benzoic acid and a carboxylate-rich peptoid.

Allosteric Effect of Adenosine Triphosphate on Peptide Recognition by 3'5'-Cyclic Adenosine Monophosphate Dependent Protein Kinase Catalytic Subunits.

The allosteric influence of adenosine triphosphate (ATP) on the binding effectiveness of a series of peptide inhibitors with the catalytic subunit of 3'5'-cyclic adenosine monophosphate dependent protein kinase was investigated, and the dependence of this effect on peptide structure was analyzed. The allosteric effect was calculated as ratio of peptide binding effectiveness with the enzyme-ATP complex and with the free enzyme, quantified by the competitive inhibition of the enzyme in the presence of ATP excess, and by the enzyme-peptide complex denaturation assay, respectively It was found that the principle "better binding-stronger allostery" holds for interactions of the studied peptides with the enzyme, indicating that allostery and peptide binding with the free enzyme are governed by the same specificity pattern. This means that the allosteric regulation does not include new ligand-protein interactions, but changes the intensity (strength) of the interatomic forces that govern the complex formation in the case of each individual ligand.

Experimental Basicities of Superbasic Phosphonium Ylides and Phosphazenes.

Experimental basicities of some of the strongest superbases ever measured (phosphonium ylides) are reported, and by employing these compounds, the experimental self-consistent basicity scale of superbases in THF, reaching a pKα (estimate of pKa) of 35 and spanning more than 30 pKa units, has been compiled. Basicities of 47 compounds (around half of which are newly synthesized) are included. The solution basicity of the well-known t-Bu-N═P4(dma)9 phosphazene superbase is now rigorously linked to the scale.

Covalent attachment of polymeric monolith to polyether ether ketone (PEEK) tubing.

A new method of reproducible preparation of vinylic polymeric monolithic columns with a key step of covalently anchoring the monolith to PEEK surface is described. In order to chemically attach the polymer monolith to the tube wall, methacrylate functional groups were introduced onto PEEK surface by a three-step procedure, including surface etching, surface reduction and surface methacryloylation. The chemical state of the modified tubing surface was characterized by attenuated total reflectance infrared (ATR-IR) spectroscopy.

2,5-Dihydroxybenzoic acid solution in MALDI-MS: ageing and use for mass calibration.

2,5-Dihydroxybenzoic acid (DHB) is one of the most widely used and studied matrix compounds in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. However, the influence of ageing of the DHB solution on the MALDI mass spectra has not been yet systematically studied. In this work, the possible changes occurring in the acidified acetonitrile/water solution of the MALDI matrix compound DHB during 1-year usage period have been monitored with MALDI-Fourier transform ion cyclotron resonance mass spectrometer (MALDI-FT-ICR-MS) and attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy.

Alternative eluent composition for LC-MS analysis of perfluoroalkyl acids in raw fish samples.

A wide range of anthropogenic pollutants that possess serious environmental and health risks are known. One type of these harmful substances that have become a focus of interest during the past decade are perfluoroalkyl acids (PFAAs), which are extensively used in industry for different purposes. Due to the harmful effects that these compounds might cause in living organisms, EFSA and EU CONTAM panel have issued a monitoring program for PFAAs in foodstuffs.

NMR method for simultaneous host-guest binding constant measurement.

An NMR-based relative binding affinity measurement method has been developed in which differences in the binding affinities of different hosts toward a particular guest (ΔlogK(ass) values) are measured in the same solution. As an advancement, the method allows the simultaneous determination of several ΔlogK(ass) values in a single run. As a proof of principle, the method was used to measure binding affinity differences of a number of indolocarbazole- and urea-based synthetic receptors toward acetate ion in DMSO-d6/H2O (99.

Accurate method to quantify binding in supramolecular chemistry.

An approach for accurate and comparable measurement of host-guest binding affinities is introduced whereby differences in binding strength (ΔlogKass values) are measured between two host molecules toward a particular guest under identical solvent conditions. Measuring differences instead of absolute values enables obtaining highly accurate results, because many of the uncertainty sources (the solvation/association state of the guest in solution, deviations in solvent composition, etc.) cancel out.

Analysis of dammar resin with MALDI-FT-ICR-MS and APCI-FT-ICR-MS.

Comprehensive analysis of high-resolution mass spectra of aged natural dammar resin obtained with Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS) using matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure chemical ionization (APCI) is presented. Dammar resin is one of the most important components of painting varnishes. Dammar resin is a terpenoid resin (dominated by triterpenoids) with intrinsically very complex composition.