Создание синтетического аналога интерлейкина-4

Целью исследовательской работы является описание методики создания синтетическогоаналога человеческого интерлейкина- 4, который будет использован для нанесения на поверхность биоматериалов на основе биодеградируемых полимеров с целью придания иммуномодулирующих свойств и увеличения биосовместимости

New aminophosphonates (aminophosphine oxides) containing acetal groups in reactions with polyatomic phenols

© 2016 Taylor & Francis Group, LLC.A wide range of phosphorylated α-,β-,γ-aminoacetals of various structure were obtained by Kabachnik- Fields reaction. Acid-catalyzed reactions of phenols with α-,β-,γ -aminoacetals provide a new approach to the synthesis of different polyphenols, containing aminophosphonate and aminophosphine oxide moieties, arylsubstituted heterocycles containing phosphonate and phosphinoxide groups. Herein we present a short overview of these reactions

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Axotomy-induced changes in the properties of NMDA receptor channels in rat spinal cord motoneurons

Properties of N-methyl-d-aspartate (NMDA) receptor channels were studied using the patch-clamp technique in fluorescence-labelled control and axotomised motoneurons in thin spinal cord slices. Single-channel currents induced by NMDA in outside-out patches isolated from axotomised motoneurons and voltage clamped at −100 mV, exhibited six amplitude levels with a mean conductance of 14.9 ± 1.9, 22.2 ± 2.7, 35.6 ± 4.4, 49.1 ± 3.5, 59.6 ± 3.5 and 69.0 ± 2.9 pS. In contrast, the conductance of NMDA receptor channels, recorded under identical conditions in control motoneurons was characterised by only four levels corresponding to 20.1 ± 2.5, 38.0 ± 3.0, 58.6 ± 3.4 and 71.5 ± 2.6 pS. The time course of deactivation of NMDA receptor EPSCs in axotomised motoneurons voltage clamped at +40 mV was double exponential. The deactivation had a similar time course in control and axotomised motoneurons from 6–day-old animals; however, the deactivation became faster with increased time after injury. The fast and slow time constants in motoneurons 8 days after axotomy became three times faster than in controls. NMDA receptor-mediated responses were voltage dependent in the presence of extracellular Mg2+. In axotomised motoneurons Boltzmann analysis of the relationship between the peak amplitude of NMDA receptor EPSCs or NMDA-induced responses and membrane potential suggested an apparent Kd for Mg2+ binding (at 0 mV) of 1.2 ± 0.5 and 3.4 ± 3.9 mm, respectively. Single-cell RT-PCR analysis of mRNA revealed that NR2A–D and NR3A subunit transcripts were expressed in axotomised motoneurons. The results of our experiments suggest that in addition to genotypic control of NMDA receptors in motoneurons, axotomy, an experimental model of neurodegeneration, alters functional properties of the receptors in motoneurons destined to die

New aminophosphonates (aminophosphine oxides) containing acetal groups in reactions with polyatomic phenols

© 2016 Taylor & Francis Group, LLC.A wide range of phosphorylated α-,β-,γ-aminoacetals of various structure were obtained by Kabachnik- Fields reaction. Acid-catalyzed reactions of phenols with α-,β-,γ -aminoacetals provide a new approach to the synthesis of different polyphenols, containing aminophosphonate and aminophosphine oxide moieties, arylsubstituted heterocycles containing phosphonate and phosphinoxide groups. Herein we present a short overview of these reactions

New aminophosphonates (aminophosphine oxides) containing acetal groups in reactions with polyatomic phenols

© 2016 Taylor & Francis Group, LLC.A wide range of phosphorylated α-,β-,γ-aminoacetals of various structure were obtained by Kabachnik- Fields reaction. Acid-catalyzed reactions of phenols with α-,β-,γ -aminoacetals provide a new approach to the synthesis of different polyphenols, containing aminophosphonate and aminophosphine oxide moieties, arylsubstituted heterocycles containing phosphonate and phosphinoxide groups. Herein we present a short overview of these reactions

New aminophosphonates (aminophosphine oxides) containing acetal groups in reactions with polyatomic phenols

© 2016 Taylor & Francis Group, LLC.A wide range of phosphorylated α-,β-,γ-aminoacetals of various structure were obtained by Kabachnik- Fields reaction. Acid-catalyzed reactions of phenols with α-,β-,γ -aminoacetals provide a new approach to the synthesis of different polyphenols, containing aminophosphonate and aminophosphine oxide moieties, arylsubstituted heterocycles containing phosphonate and phosphinoxide groups. Herein we present a short overview of these reactions