(2-Arylethenyl)-1,3,5-triazin-2-amines as a novel histamine H4 receptor ligands.

Within the constantly growing number of histamine H4 (H4R) receptor ligands there is a large group of azine derivatives. A series of novel compounds in the group of 4-methylpiperazine-1,3,5-triazine-2-amines were designed and obtained. Considered structures were modified at the triazine 6-position by introduction of variously substituted arylethenyl moieties.

Crypteins--an overlooked piece of peptide systems.

Crypteins, the hidden bioactive sequences, play an important role in the modulation of various biological processes, such as neuronal signaling, angiogenesis, immune response, inflammatory response and cell growth. Proteolytic mechanism leading to the release of crypteins possessing novel biological activities is an important factor for increasing diversity of functional molecules and represents a potential new source of peptide drugs. In this work we would like to focus on crypteins derived from the already known precursors and their potential therapeutic value.

Aryl-1,3,5-triazine derivatives as histamine H4 receptor ligands.

A series of novel 2-amino-4-(4-methylpiperazin-1-yl)-1,3,5-triazine derivatives with different aryl substituents in the 6-position was designed, synthesized and evaluated for histamine H4 receptor (H4R) affinity in Sf9 cells expressing human H4R co-expressed with G-protein subunits. Triazine derivative 8 with a 6-(p-chlorophenyl) substituent showed the highest affinity with hH4R Ki value of 203 nM and was classified as an antagonist in cAMP accumulation assay. This compound, identified as a new lead structure, demonstrated also anti-inflammatory properties in preliminary studies in mice (carrageenan-induced edema test) and neither possessed significant antiproliferative activity, nor modulated CYP3A4 activity up to concentration of 25 μM.

DESI-MS as a tool for direct lipid analysis in cultured cells.

Desorption electrospray ionization may be used as a fast and convenient method for analysis and identification of lipids in the cell culture. Oxidative stress, which usually involves changes in lipids, was used as a model of pathology to show the utility of this analysis methodology. This paper addresses the surface preparation of cell culture slides, induction of oxidative stress, and cell monolayer culture preparation as well as optimization of the analysis.

Desorption electrospray ionisation (DESI) for beginners--how to adjust settings for tissue imaging.

Rationale: Desorption electrospray ionisation (DESI) is the ambient technique used for surface imaging. Despite its simplicity, the proper use of this technique is not easy, and usually leads to discouragement, especially in the case of biological sample measurements. Here, we present some tips and tricks which may be helpful during a complex process of ion source optimisation to achieve the desired results.

Dynorphin convertases and their functions in CNS.

Neuropeptides play crucial, mediatory roles in many processes that occur in both CNS and PNS. The commonly accepted dogma for the release of bioactive peptides involves cleavage of inactive precursor by sequential action of proteinases recognizing dibasic stretches, followed by truncation of C-terminal Arg/Lys by the carboxypeptidase-like enzyme(s). Dynorphin convertases play an important role in CNS by regulating dynorphins level and also releasing enkephalins, thus maintaining a balance between these neuropeptides and their distinct functions (dynorphins are preferentially bound to kappa receptors and enkephalins are directed toward delta receptors).