OBSERVATIONS ON A CHAMAESIPHONACEOIS ALGA (CYANOPHYCEAE) WITH SPECIAL REFERENCE TO EXOCYTE FORMATION1,2

A unicellular cyanophycean culture contaminant had features of both Geitleribactron Kom. and Cyanophanon Geitl. The cells were elongated, sheathless, mostly similar in diameter throughout their length, and attached polarly in rosettes or groups and produced only a single elongated exocyte (=exospore). Young cells were moderately elongated and resembled Geitleribactron. As cells aged, they greatly elongated and then resembled Cyanophanon. Some cells formed Y-shaped bifurcations, features of C. mirabile Geitl. and C. minus Geitl., but they lacked the basal sheath (pseudovagina) of C. mirabile. During exocyte formation, a thick and localized L-II wall layer protuberance extended the exocyte away from the parent cell. This terminal wall thickening then appeared to move to one side from subsequent and unequal cell wall growth. Cells sovnetimes bent abruptly, occasionally opposite a thickening in the L-II wall layer. Further studies in culture of putative Geitleribactron and Cyanophanon isolates are necessary to ascertain the breadth of their structural diversity and the identity of the present taxon.     

Solid-phase synthesis of an N-(phenylalkyl)cinnamide library via Horner-Wadsworth-Emmons reaction

A readily automated solid-phase approach to the synthesis of diverse N-(phenylalkyl)cinnamides, analogues of the NR2B antagonist 2, is described. The procedure utilizes polymer supported N-(phenylalkyl)amines, (diethylphosphono)acetic acid and a wide range of commercially available hydroxybenzaldehydes. The key step, a Horner-Wadsworth-Emmons reaction is achieved under mild conditions and was found to be general for a large number of benzaldehydes. A 225-member focused library was synthesized using a Tecan Combitec synthesizer.     

Laureates of the Palladin Premium of the National Academy of Science of Ukraine

The article presents a short information about the Resolution of Ukr.SSR Soviet of Ministers on establishing the nominal premium of Presidium the Academy of Sciences of Ukr.SSR (of NAS of Ukraine, now) in the field of biochemistry and molecular biology dedicated to the famous scientists, founder of the Ukrainian biochemical school and the Institute of Biochemistry named after him--academician O. V. Palladin. There is a chronologically sequential list presenting all Laureates (with photo pictures) awarded by this honourable bonus with displaying their scientific works for which they received this reward.     

Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists

Hit-to-lead optimization of a HTS hit led to new carbamoyloxime derivatives. After identification of an advanced hit (8d) the CYP enzyme inhibitory activity of this class of compounds was successfully eliminated. Systematic exploration of different parts of the advanced hit led us to some promising lead compounds with mGluR5 affinities comparable to that of MPEP.     

Hit-to-lead optimization of disubstituted oxadiazoles and tetrazoles as mGluR5 NAMs

Here we report the discovery and early SAR of a series of mGluR5 negative allosteric modulators (NAMs). Starting from a moderately active HTS hit we synthesized 3,5-disubstituted-oxadiazoles and tetrazoles as mGluR5 NAMs. Based on the analysis of ligand efficiency and lipophilic efficiency metrics we identified a promising lead candidate as a starting point for further optimization.     

Identification and characterization of protein glycosylation using specific endo- and exoglycosidases

Glycosylation, the addition of covalently linked sugars, is a major post-translational modification of proteins that can significantly affect processes such as cell adhesion, molecular trafficking, clearance, and signal transduction. In eukaryotes, the most common glycosylation modifications in the secretory pathway are additions at consensus asparagine residues (N-linked); or at serine or threonine residues (O-linked) (Figure 1). Initiation of N-glycan synthesis is highly conserved in eukaryotes, while the end products can vary greatly among different species, tissues, or proteins. Some glycans remain unmodified ("high mannose N-glycans") or are further processed in the Golgi ("complex N-glycans"). Greater diversity is found for O-glycans, which start with a common N-Acetylgalactosamine (GalNAc) residue in animal cells but differ in lower organisms. The detailed analysis of the glycosylation of proteins is a field unto itself and requires extensive resources and expertise to execute properly. However a variety of available enzymes that remove sugars (glycosidases) makes possible to have a general idea of the glycosylation status of a protein in a standard laboratory setting. Here we illustrate the use of glycosidases for the analysis of a model glycoprotein: recombinant human chorionic gonadotropin beta (hCGβ), which carries two N-glycans and four O-glycans. The technique requires only simple instrumentation and typical consumables, and it can be readily adapted to the analysis of multiple glycoprotein samples. Several enzymes can be used in parallel to study a glycoprotein. PNGase F is able to remove almost all types of N-linked glycans. For O-glycans, there is no available enzyme that can cleave an intact oligosaccharide from the protein backbone. Instead, O-glycans are trimmed by exoglycosidases to a short core, which is then easily removed by O-Glycosidase. The Protein Deglycosylation Mix contains PNGase F, O-Glycosidase, Neuraminidase (sialidase), β1-4 Galactosidase, and β-N-Acetylglucosaminidase. It is used to simultaneously remove N-glycans and some O-glycans. Finally, the Deglycosylation Mix was supplemented with a mixture of other exoglycosidases (α-N-Acetylgalactosaminidase, α1-2 Fucosidase, α1-3,6 Galactosidase, and β1-3 Galactosidase), which help remove otherwise resistant monosaccharides that could be present in certain O-glycans. SDS-PAGE/Coomasie blue is used to visualize differences in protein migration before and after glycosidase treatment. In addition, a sugar-specific staining method, ProQ Emerald-300, shows diminished signal as glycans are successively removed. This protocol is designed for the analysis of small amounts of glycoprotein (0.5 to 2 μg), although enzymatic deglycosylation can be scaled up to accommodate larger quantities of protein as needed.     

O. V. Palladin--patriarch of neurochemical science (on the 120th birthday of academician Oleksandr Volodymyrovych Palladin)

The paper is dedicated to Academician Oleksandr Volodymyrovych Palladin (1895-1972), a founder of neurochemical school in Ukraine. The problem of biochemistry of the nervous system has been developed in Ukraine since the 20's of the 20th century. Theoretical principles and prospects of development of the basic trends in neurochemistry were stated for the first time in the paper by O. V. Palladin--the first work in biochemistry of the nervous system in Ukraine--"Biochemistry of the Brain and Psychochemistry", published in the journal "Nauka v Ukraine" ("Science in Ukraine") in 1922. Researches in neurochemistry have been carried out systematically since 1925 at the Ukrainian Biochemical Institute founded and headed by O. V. Palladin (O. V. Palladin Institute of Biochemistry, now). During the following period of half a century O.V.Palladin and his disciples made original works in the field of chemical topography of the nervous system, functional neurochemistry, in particular, in the field of protein and nitrous, lipid, nucleic metabolism, transmembrane transport of ions and metabolites, etc. Results of long-term investigations were reported at numerous international physiological and biochemical congresses, All-Union and Ukrainian biochemical conferences, seminars and have acquired the world fame. O. V. Palladin's great deserts in development of biochemistry of the nervous system were recognized and he was proclaimed a "patriarch" of the world neurochemistry at the first congress of the International Neurochemical Society in Strassburg (1967) and awarded a Gold Medal--one of the four delivered at the Second Congress of this Society in Milan (1969).     

O.V. Palladin Institute of Biochemistry of the Ukrainian National Academy of Sciences--75 years

The article deals with a short record including the information about the history of creation and main developmental stages of the first and presently the single in Ukraine Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine. The record contains the main achievements of the Institute scientific subdivisions for the 75 years period of their creative work in the field of the most urgent problems of fundamental and applied biochemistry. As well it displays the information about comprehensive and extensive publishing and educational activity conducted by the staff,, the work on training the scientific manpower of the highest qualification--Doctors of Science (D.Sc.) and Philosophy Doctors (Ph. D.), active participation of the research scientists in attracting to science the talented young people representing the students and school-children taking interest in the biological chemistry. The article shows the great role of the Institute famous scientists-biochemists in forming some scientific schools on functional biochemistry acknowledged in the world biochemistry. There are also some data about the each of nine scientific departments of the Institute for the period of last 20-25 years of their activity in the field of the most urgent problems of the contemporary biochemistry. These are the following Departments: Neurochemistry, Metabolism Regulation, Muscular Biochemistry, Protein Structure Functions, Coenzymes Biochemistry, Enzymes Chemistry and Biochemistry, Molecular Immunology, Biochemistry of Lipids, Sensor and Regulator Systems Biochemistry. There is also a short review regarding the history of foundation, development and scientific achievements of the Institute division in L'viv including four scientific departments: Biochemistry of Cellular Differentiation, Biochemical Genetics, Regulation of Low Molecular Compounds Synthesis, Regulation of Cells Differentiation.     

Novel sulfonamides having dual dopamine D2 and D3 receptor affinity show in vivo antipsychotic efficacy with beneficial cognitive and EPS profile

A novel series of arylsulfonamides was prepared either by automated parallel or by traditional solution-phase synthesis. Several members of this compound library were identified as high-affinity dopamine D3 and D2 receptor ligands. The most interesting representative, compound 2, showed potent antipsychotic behaviour coupled with a beneficial cognitive and EPS profile.