In silico and in vivo neuropharmacological evaluation of two γ-amino acid isomers derived from 2,3-disubstituted benzofurans, as ligands of GluN1–GluN2A NMDA receptor

Amino Acids ◽  
2021 ◽  
Author(s):  
Arturo Coaviche-Yoval ◽  
José G. Trujillo-Ferrara ◽  
Marvin A. Soriano-Ursúa ◽  
Erik Andrade-Jorge ◽  
Luis A. Sánchez-Labastida ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
In Silico

In-silico structural, functional and immunogenic characterization of Taenia solium TS14 protein

2017 ◽  
Author(s):  
Chitra Joshi ◽  
Siddharth Gautam
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Mutational Analysis ◽  
Solvent Accessibility ◽  
Taenia Solium ◽  
Secretory Protein ◽  
Single Amino Acid

TS14, a Cysticercosis cellulosae derived protein, has been exploited for immunodiagnosis of cysticercosis in humans and pigs. However, the information on structure, function, stability and immunogenicity of TS14 derived from different isolates is primarily lacking. The present study deals with in-silico characterization of six TS14 isolates. High thermostability and an isoelectric point of 9.41 were recorded. Based on N-terminal amino acid residues, high resistance to intracellular proteases with extended in-vivo and in-vitro half-lives was predicted. TS14 is foreseen as a secretory protein with a signal peptide and an extracellular localization. Structural analysis of TS14 exhibited the dominance of helices in the secondary structure (92% coverage) with majority of residues showing high and medium solvent accessibility. High lysine content and presence of multiple nucleotide binding sites in TS14 suggests interaction with RNA/DNA and a role in their metabolism. Immunogenic profiling predicted presence of four distinct B-cell epitopes. Mutational analysis based on the single amino acid substitutions among six TS14 isolates demonstrated minor variations in structural stability; however, all the substitutions were well tolerated. Moreover, all the isolates revealed almost identical immunogenic profile with an equivocal potential to elicit the antibody-mediated immune response.

Antagonism of N-methyl-D-aspartate (NMDA) evoked increases in cerebellar cGMP and striatal ACh release by phencyclidine (PCP) receptor agonists; evidence for possible allosteric coupling of NMDA and PCP receptors

1987 ◽  
Vol 65 (9) ◽  
pp. 1923-1927 ◽  
Author(s):  
Paul L. Wood ◽  
Douglas Steel ◽  
Stephen E. McPherson ◽  
Darwin L. Cheney ◽  
John Lehmann
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Excitatory Amino Acid ◽  
Cell Activity ◽  
Allosteric Coupling ◽  
Receptor Agonists ◽  
Cholinergic Interneurons ◽  
Neuronal Systems

A comparison was made of the actions of phencyclidine receptor agonists and N-methyl-D-aspartate (NMDA) receptor antagonists in two well-defined neurochemical test systems. These included (i) [3H]acetylcholine release from striatal cholinergic interneurons in vitro, a system known to be positively modulated by corticostriatal excitatory amino acid inputs in vivo; and (ii) cerebellar cGMP levels in vivo, an indicator of cerebellar Purkinje cell activity, which is also modulated by excitatory amino acid inputs. Using these neuronal systems, we report that phencyclidine receptor agonists demonstrated a noncompetitive antagonism of NMDA receptor agonist actions.

scholarly journals ASCT1 (Slc1a4) transporter is a physiologic regulator of brain d-serine and neurodevelopment

2018 ◽  
Vol 115 (38) ◽  
pp. 9628-9633 ◽  
Author(s):  
Eitan Kaplan ◽  
Salman Zubedat ◽  
Inna Radzishevsky ◽  
Alec C. Valenta ◽  
Ohad Rechnitz ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Motor Function ◽  
In Vivo Microdialysis ◽  
Therapeutic Interventions ◽  
Uptake System ◽  
Affective Behavior ◽  
Serine Metabolism ◽  
Metabolic Impairments

d-serine is a physiologic coagonist of NMDA receptors, but little is known about the regulation of its synthesis and synaptic turnover. The amino acid exchangers ASCT1 (Slc1a4) and ASCT2 (Slc1a5) are candidates for regulating d-serine levels. Using ASCT1 and ASCT2 KO mice, we report that ASCT1, rather than ASCT2, is a physiologic regulator of d-serine metabolism. ASCT1 is a major d-serine uptake system in astrocytes and can also export l-serine via heteroexchange, supplying neurons with the substrate for d-serine synthesis. ASCT1-KO mice display lower levels of brain d-serine along with higher levels of l-alanine, l-threonine, and glycine. Deletion of ASCT1 was associated with neurodevelopmental alterations including lower hippocampal and striatal volumes and changes in the expression of neurodevelopmental-relevant genes. Furthermore, ASCT1-KO mice exhibited deficits in motor function, spatial learning, and affective behavior, along with changes in the relative contributions of d-serine vs. glycine in mediating NMDA receptor activity. In vivo microdialysis demonstrated lower levels of extracellular d-serine in ASCT1-KO mice, confirming altered d-serine metabolism. These alterations are reminiscent of some of the neurodevelopmental phenotypes exhibited by patients with ASCT1 mutations. ASCT1-KO mice provide a useful model for potential therapeutic interventions aimed at correcting the metabolic impairments in patients with ASCT1 mutations.

Mechanisms of action of antihyperglycemic mexicanolides isolated from Swietenia humillis: in vivo and in silico approaches

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381 ◽  
Author(s):  
B Ovalle-Magallanes ◽  
A Madariaga-Mazón ◽  
A Navarrete ◽  
R Mata
Keyword(s):  
In Silico ◽  
Mechanisms Of Action

Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using in silico Method

2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Plasmodium Species ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Sequence ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range of hosts including humans and rodents. There are two copies of mitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise of presented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series of publicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localized and contain both a nuclear localization signal (NLS) and a Leucine-rich nuclear export signal (NES). The activation motifs of TDY and TSH were found to be fully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection of a multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising of different amino acids present in MAPKJ and MAPK2 respectively, with respect to rodent and human Plasmodia. It is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs. 

Comparative Study on Mitogen Activated Protein Kinase of Plasmodium Species by Using In silico Method

2012 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Mohd Fakharul Zaman Raja Yahya ◽  
Hasidah Mohd Sidek
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Nuclear Export ◽  
Nuclear Export Signal ◽  
Plasmodium Species ◽  
Mitogen Activated Protein Kinase ◽  
Multiple Sequence ◽  
Bioinformatic Tools ◽  
Wide Range ◽  
Human Plasmodium

Malaria parasites, Plasmodium can infect a wide range ofhosts including humans and rodents. There are two copies ofmitogen activated protein kinases (MAPKs) in Plasmodium, namely MAPK1 and MAPK2. The MAPKs have been studied extensively in the human Plasmodium, P. falciparum. However, the MAPKs from other Plasmodium species have not been characterized and it is therefore the premise ofpresented study to characterize the MAPKs from other Plasmodium species-P. vivax, P. knowlesi, P. berghei, P. chabaudi and P.yoelli using a series ofpublicly available bioinformatic tools. In silico data indicates that all Plasmodium MAPKs are nuclear-localizedandcontain both a nuclear localization signal (NLS) anda Leucine-rich nuclear export signal (NES). The activation motifs ofTDYand TSH werefound to befully conserved in Plasmodium MAPK1 and MAPK2, respectively. The detailed manual inspection ofa multiple sequence alignment (MSA) construct revealed a total of 17 amino acid stack patterns comprising ofdifferent amino acids present in MAPK1 and MAPK2 respectively, with respect to rodent and human Plasmodia. 1t is proposed that these amino acid stack patterns may be useful in explaining the disparity between rodent and human Plasmodium MAPKs.

Ruthenium Complexes for 1- and 2-Photon Photodynamic Therapy: From In Silico Prediction to In Vivo Applications

2020 ◽  
Author(s):  
Johannes Karges ◽  
Shi Kuang ◽  
Federica Maschietto ◽  
Olivier Blacque ◽  
Ilaria Ciofini ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
In Silico ◽  
Aqueous Solubility ◽  
The Body ◽  
Photon Absorption ◽  
Multicellular Tumor Spheroids ◽  
Spectral Window ◽  
Photon Excitation ◽  
Polypyridine Complexes

<div>The use of photodynamic therapy (PDT) against cancer has received increasing attention overthe recent years. However, the application of the currently approved photosensitizers (PSs) is somehow limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E’)-4,4´-bisstyryl 2,2´-bipyridine ligands showed impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While non-toxic in the dark, these compounds were found phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and be able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2 Photon excitation.</div>

Site Specific Incorporation of Amino Acid Analogues into Proteins In Vivo

2000 ◽  
Author(s):  
Anne K. Kowal ◽  
Caroline Kohrer ◽  
Uttam L. RajBhandary
Keyword(s):  
Amino Acid ◽  
Site Specific ◽  
Amino Acid Analogues
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