scholarly journals Hydrolytic Stability of New Amino Acids Analogues of Memantine

2020 ◽  
Vol 88 (3) ◽  
pp. 38
Author(s):  
Aleksandra Tencheva ◽  
Radoslav Chayrov ◽  
Petko Mandjukov ◽  
Dancho Danalev ◽  
Ivanka Stankova
Keyword(s):  
Amino Acids ◽  
Blood Circulation ◽  
Hydrolytic Stability ◽  
Kinetic Studies ◽  
Neutral Medium ◽  
Aspartate Receptor ◽  
Biological Liquids ◽  
The Stability ◽  
Active Fragment ◽  
Lipid Barriers

In the present work, the hydrolytic stability of new memantine analogues modified with amino acids, at different pH corresponding to the human biological liquids and organs, was evaluated. Memantine is an uncompetitive N-methyl-d-aspartate receptor antagonist with low-to moderate-affinity. In addition, it is the first representative of a novel class of Alzheimer’s disease (AD) medications acting on the glutamatergic system by blocking N-methyl-D-aspartate receptors. Generally, prodrugs are compounds aiming to improve stability of active fragment and to facilitate transportation across the cell membranes or lipid barriers. The investigated series of prodrugs include modified memantine with the following amino acids: alanine, β-alanine, glycine, phenylalanine, and valine. Hydrolytic stability was determined at two different pH values 2.0 and 7.4 at 37 °C, similar to those in the human stomach and blood plasma. Specially developed UV-VIS spectrophotometric method for quantification of the concentrations of unchanged compounds was applied in the kinetic studies. Val-MEM is the most stable in neutral medium and at 37 °C compound with t1/2 = 50.2 h. The compound Phe-MEM has also very good hydrolytic stability with t1/2 = 29.6 h. The order of other compounds is: Val-MEM ≫ Phe-MEM ≫ Ala-MEM ≈ Val-MEM > β-Ala-MEM. Ala-MEM and Gly-MEM are the most stable compounds at acid condition with almost identical values for t1/2 = 17.8 h and t1/2 = 16.3 h, respectively. The stability of tested compounds in acid conditions are relatively less than in neutral one. They are ordered as follows: Ala-MEM ≈ Gly-MEM > Val-MEM ≈ Phe-MEM ≈ β-Ala-MEM. All compounds have relatively good hydrolytic stability of more than 10 h at both neutral and acid conditions, which is quite enough in order to pass in the blood circulation and to be used as a potential antimicrobial agent.

scholarly journals COPIGMENTAÇÃO INTRA E INTERMOLECULAR DE ANTOCIANINAS: UMA REVISÃO

2003 ◽  
Vol 21 (2) ◽  
Author(s):  
LEILA D. FALCÃO ◽  
DENISE M. BARROS ◽  
CONY GAUCHE ◽  
MARILDE T. BORDIGNON LUIZ
Keyword(s):  
Amino Acids ◽  
Literature Review ◽  
The Stability

Este trabalho apresenta revisão de literatura sobre a reação de copigmentação intra e intermolecular e sua relevância na estabilização de antocianinas. Flavonóides não-antociânicos, alcalóides, aminoácidos e nucleosídios, entre outros, podem atuar como copigmentos de antocianinas. O aumento na estabilidade das antocianinas ocorre devido à proteção fornecida pelo copigmento frente à reação de hidratação do cátion flavilium. Estudos ainda são necessários para avaliar a estabilidade de antocianinas adicionadas de copigmentos em sistemas modelos de alimentos, visando aumentar o espectro de aplicação dessas como corantes em alimentos e bebidas. ANTHOCYANINS INTRA AND INTERMOLECULAR COPIGMENTATION: A REVIEW Abstract This research presents literature review about the reaction of intra and intermolecular copigmentation and its revealance in anthocyanins stabilization. Non-anthocyanic flavonoids, alkaloids, amino acids, nucleosides, and others, can act as anthocyanins copigments. The increase in the stability of anthocyanins occurs due to protection supplied by the copigment towards the hydratation reaction of colored flavylium cation. Studies to evaluate anthocyanins stabilization added of copigments in food models system are still necessary, aiming to enhance the application spectra as colorants in foods and beverages.

scholarly journals H-2M3a violates the paradigm for major histocompatibility complex class I peptide binding.

1995 ◽  
Vol 181 (5) ◽  
pp. 1817-1825 ◽  
Author(s):  
J M Vyas ◽  
J R Rodgers ◽  
R R Rich
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Temperature Shift ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Compensatory Adaptation ◽  
Chemotactic Peptides ◽  
The Stability ◽  
Formyl Peptides

The major histocompatibility (MHC) class I-b molecule H-2M3a binds and presents N-formylated peptides to cytotoxic T lymphocytes. This requirement potentially places severe constraints on the number of peptides that M3a can present to the immune system. Consistent with this idea, the M3a-Ld MHC class I chimera is expressed at very low levels on the cell surface, but can be induced significantly by the addition of specific peptides at 27 degrees C. Using this assay, we show that M3a binds many very short N-formyl peptides, including N-formyl chemotactic peptides and canonical octapeptides. This observation is in sharp contrast to the paradigmatic size range of peptides of 8-10 amino acids binding to most class I-a molecules and the class I-b molecule Qa-2. Stabilization by fMLF-benzyl amide could be detected at peptide concentrations as low as 100 nM. While N-formyl peptides as short as two amino acids in length stabilized expression of M3a-Ld, increasing the length of these peptides added to the stability of peptide-MHC complexes as determined by 27-37 degrees C temperature shift experiments. We propose that relaxation of the length rule may represent a compensatory adaptation to maximize the number of peptides that can be presented by H-2M3a.

scholarly journals Real-time kinetic studies of Mycobacterium tuberculosis LexA-DNA interaction

2021 ◽  
Author(s):  
Chitral Chatterjee ◽  
Soneya Majumdar ◽  
Sachin Deshpande ◽  
Deepak Pant ◽  
Saravanan Matheshwaran
Keyword(s):  
Amino Acids ◽  
Mycobacterium Tuberculosis ◽  
Dna Binding ◽  
Kinetic Parameters ◽  
Dna Sequences ◽  
Kinetic Studies ◽  
Dna Interaction ◽  
Damage Repair ◽  
Inducible Genes ◽  
Kinetics Of

Transcriptional repressor, LexA, regulates the “SOS” response, an indispensable bacterial DNA damage repair machinery.  Compared to its E.coli ortholog, LexA from Mycobacterium tuberculosis (Mtb) possesses a unique N-terminal extension of additional 24 amino acids in its DNA binding domain (DBD) and 18 amino acids insertion at its hinge region that connects the DBD to the C-terminal dimerization/autoproteolysis domain. Despite the importance of LexA in “SOS” regulation, Mtb LexA remains poorly characterized and the functional importance of its additional amino acids remained elusive. In addition, the lack of data on kinetic parameters of Mtb LexA-DNA interaction prompted us to perform kinetic analyses of Mtb LexA and its deletion variants using Bio-layer Interferometry (BLI). Mtb LexA is seen to bind to different “SOS” boxes, DNA sequences present in the operator regions of damage-inducible genes, with comparable nanomolar affinity. Deletion of 18 amino acids from the linker region is found to affect DNA binding unlike the deletion of the N-terminal stretch of extra 24 amino acids. The conserved RKG motif has been found to be critical for DNA binding. Overall, this study provides insights into the kinetics of the interaction between Mtb LexA and its target “SOS” boxes. The kinetic parameters obtained for DNA binding of Mtb LexA would be instrumental to clearly understand the mechanism of “SOS” regulation and activation in Mtb.

scholarly journals Thermal stability of amino acids in meals and feeds used in shrimp farming

Gaia Scientia ◽  
2016 ◽  
Vol 10 (4) ◽  
pp. 372-389
Author(s):  
João Paulo de Sousa Prado ◽  
José Marcelino Oliveira Cavalheiro ◽  
Thiago Brandão Cavalheiro ◽  
Fernanda Vanessa Gomes da Silva
Keyword(s):  
Amino Acids ◽  
Elevated Temperatures ◽  
Amino Acid Content ◽  
Storage Conditions ◽  
Shrimp Farming ◽  
Protein Levels ◽  
Commercial Feed ◽  
The Stability ◽  
The Right ◽  
And Control

The Brazilian shrimp farming uses mainly commercial feed for shrimp nutrition. This choice occurs because of the advantages related to convenience and good adaptation of Litopenaeus vannanmei to feed intake. Thus, the quality of feed is a determining factor for maximum performance of the shrimp farms, making the right selection of suppliers and control of the storage conditions as ways to prevent contamination and spoilage of feed. The objective of this study was to evaluate the stability of amino acids in meals and commercial feed with different protein levels, subjected to high-temperature storage. The samples were exposed to temperature of 50 oC and evaluated every 5 days for 30 days.The analyses of the degradation of amino acids were performed using an elution gradient in HPLC system.In evaluated meals it was observed that valine and arginine were the amino acids that suffered greater loss during the experiment and histidine and alanine suffered less degradation.Significant difference was observed in the content of all amino acids analyzed after exposure of the feed to the temperature of 50 oC; with reduce in values of its amino acid content. The results obtained in this study indicate that meals and feed exposed to elevated temperatures significantly reduced the content of its amino acids.

scholarly journals Presenilin1 familial Alzheimer disease mutants inactivate EFNB1- and BDNF-dependent neuroprotection against excitotoxicity by affecting neuroprotective complexes of N-methyl-d-aspartate receptor

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Md Al Rahim ◽  
Yonejung Yoon ◽  
Christina Dimovasili ◽  
Zhiping Shao ◽  
Qian Huang ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
De Novo ◽  
Neuronal Damage ◽  
Trophic Factors ◽  
Presenilin 1 ◽  
Wild Type ◽  
Receptor Complexes ◽  
Aspartate Receptor ◽  
Familial Alzheimer Disease ◽  
The Stability

Abstract Excitotoxicity is thought to play key roles in brain neurodegeneration and stroke. Here we show that neuroprotection against excitotoxicity by trophic factors EFNB1 and brain-derived neurotrophic factor (called here factors) requires de novo formation of ‘survival complexes’ which are factor-stimulated complexes of N-methyl-d-aspartate receptor with factor receptor and presenilin 1. Absence of presenilin 1 reduces the formation of survival complexes and abolishes neuroprotection. EPH receptor B2- and N-methyl-d-aspartate receptor-derived peptides designed to disrupt formation of survival complexes also decrease the factor-stimulated neuroprotection. Strikingly, factor-dependent neuroprotection and levels of the de novo factor-stimulated survival complexes decrease dramatically in neurons expressing presenilin 1 familial Alzheimer disease mutants. Mouse neurons and brains expressing presenilin 1 familial Alzheimer disease mutants contain increased amounts of constitutive presenilin 1–N-methyl-d-aspartate receptor complexes unresponsive to factors. Interestingly, the stability of the familial Alzheimer disease presenilin 1–N-methyl-d-aspartate receptor complexes differs from that of wild type complexes and neurons of mutant-expressing brains are more vulnerable to cerebral ischaemia than neurons of wild type brains. Furthermore, N-methyl-d-aspartate receptor-mediated excitatory post-synaptic currents at CA1 synapses are altered by presenilin 1 familial Alzheimer disease mutants. Importantly, high levels of presenilin 1–N-methyl-d-aspartate receptor complexes are also found in post-mortem brains of Alzheimer disease patients expressing presenilin 1 familial Alzheimer disease mutants. Together, our data identify a novel presenilin 1-dependent neuroprotective mechanism against excitotoxicity and indicate a pathway by which presenilin 1 familial Alzheimer disease mutants decrease factor-depended neuroprotection against excitotoxicity and ischaemia in the absence of Alzheimer disease neuropathological hallmarks which may form downstream of neuronal damage. These findings have implications for the pathogenic effects of familial Alzheimer disease mutants and therapeutic strategies.

scholarly journals Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics

Amino Acids ◽  
2020 ◽  
Vol 52 (9) ◽  
pp. 1207-1226
Author(s):  
Yun Ding ◽  
Joey Paolo Ting ◽  
Jinsha Liu ◽  
Shams Al-Azzam ◽  
Priyanka Pandya ◽  
...  
Keyword(s):  
Amino Acids ◽  
Its Sequence ◽  
Peptide Therapeutics ◽  
Large Proteins ◽  
Drug Candidates ◽  
Ongoing Development ◽  
The Stability ◽  
Natural Amino Acids ◽  
The Impact ◽  
As Toxicity

Abstract With the development of modern chemistry and biology, non-proteinogenic amino acids (NPAAs) have become a powerful tool for developing peptide-based drug candidates. Drug-like properties of peptidic medicines, due to the smaller size and simpler structure compared to large proteins, can be changed fundamentally by introducing NPAAs in its sequence. While peptides composed of natural amino acids can be used as drug candidates, the majority have shown to be less stable in biological conditions. The impact of NPAA incorporation can be extremely beneficial in improving the stability, potency, permeability, and bioavailability of peptide-based therapies. Conversely, undesired effects such as toxicity or immunogenicity should also be considered. The impact of NPAAs in the development of peptide-based therapeutics is reviewed in this article. Further, numerous examples of peptides containing NPAAs are presented to highlight the ongoing development in peptide-based therapeutics.

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