Excitatory amino acids

Moloney, Mark G.

doi:10.1039/a815205y

Cited by 112 publications

(33 citation statements)

References 107 publications

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“…The parameters a (1) and a (2) are distances that are relatively highly varied within the pharmacophore, a (3) and a (4) describe the location of the fourth oxygen if present in the compound, a (5) and a (6) characterize the locations of the hydrophobic regions, while a (7) stands for the interaction index of the oxygen O2 atom. The distance of the hydrophobic regions are taken from the farthest carbon atom plus 1.5 Å to take into account the C2 2H distance and the van der Waals radius of hydrogen.…”

Section: Pharmacophore Flexibility and Anti-pharmacophore Shielding Imentioning

confidence: 99%

“…Illustration to the parameterization of the AG groups in (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (T6) with the pharmacophore atoms highlighted. The two hydrophobic groups H I and H II are characterized by their distances from the pharmacophore centroid (*) and O3, respectively; the position of the O4 atom enters in two parameters, a (3) and a (4) . decreases, and it is suggested [20] that if N > 0.4, the model with N parameters is doing no better than that with N 7 1.…”

Section: Quantitative Prediction and Cross-validationmentioning

confidence: 99%

“…Group II includes mGluR2 and mGluR3, and Group III includes mGluR4, mGluR6, mGluR7, and mGluR8; both Group II and Group III inhibit adenylyl cyclase activity [4,5]. Metabotropic glutamate receptors are believed to play an important role in many chronic or neurodegenerative diseases such as pain, epilepsy, ischemia, schizophrenia, and Alzheimer's disease [1,4,6]. It is for this reason that the ability to target each individual receptor is very important.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacophore Identification and Bioactivity Prediction for Group I Metabotropic Glutamate Receptor Agonists by the Electron-Conformational QSAR Method

Rosines¹,

Берсукер²,

Boggs³

2001

Quant. Struct.-Act. Relat.

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The pharmacophore for group I metabotropic glutamate receptor (mGluR1) agonists is revealed and their activity predicted by means of the previously developed and further improved electron-conformational (EC) method. A distinguishing feature of this method is that in addition to revealing the pharmacophore of activity as a set of specific atomic electronic features arranged in a special geometry, it allows for prediction of the activity quantitatively as a function of the parameters of pharmacophore flexibility and anti-pharmacophore shielding groups. Conformational analysis, electronic structure calculations, and matrix processing are performed for the training set of 29 compounds, 13 active and 16 inactive, and the pharmacophore of mGluR1 agonists is evaluated. It contains a four-point skeleton of three oxygen atoms and one nitrogen atom at certain interatomic distances with restricted atomic interaction indices whereby all these parameters are determined within certain tolerances. The pharmacophore parameter flexibilities, as well as the influence of the anti-pharmacophore shielding and other auxiliary groups are parameterized and weighted by seven constants, their values being obtained from a least-square regression with very good statistics: R 2 ¼ 0.97, F ¼ 589 ($100% level of confidence), and a standard error of about 5% of the range of measured values. The results are also tested with the leave-one-out crossvalidation method that yields prediction statistics R 2 ¼ 0.91. The E statistics were also evaluated illustrating the role of each of the activity parameters involved.

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Section: Pharmacophore Flexibility and Anti-pharmacophore Shielding Imentioning

confidence: 99%

Section: Quantitative Prediction and Cross-validationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacophore Identification and Bioactivity Prediction for Group I Metabotropic Glutamate Receptor Agonists by the Electron-Conformational QSAR Method

Rosines¹,

Берсукер²,

Boggs³

2001

Quant. Struct.-Act. Relat.

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“…d-Alanine levels also increase during anaerobiosis in crustaceans, suggesting that it might be an anaerobic end product under anoxia [64]. Excitatory amino acids are known to mediate synaptic excitation and, therefore, nerve signal transmission in the mammalian central nervous system by binding to several receptors [67]. In this sense, d-aspartic acid and NMDA are widely known for being agonists of the l-glutamate receptor of NMDA type in vertebrates and invertebrates, and they are involved in hormone synthesis and release [68].…”

mentioning

confidence: 98%

“…Recently, d-serine has also been shown to be an agonist of NMDA receptors, mediating several important physiological and pathological processes [9] [69] [70]. Moloney has reviewed other d-amino acids which have been established to bind some class of receptors [67], such as (R)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propanoic acid (R-APPA; competitive antagonist of the quisqualate receptor); 3,5-dihydroxyphenlyglycine (3,5-DHPG; agonist of metabotropic glutamate receptor class I), and several derivatives of d-phenylglycine (d-PG; agonists of metabotropic glutamate receptor class II and III).…”

mentioning

confidence: 99%

Natural Occurrence and Industrial Applications of d‐Amino Acids: An Overview

Martínez‐Rodríguez

Martínez-Gómez

Rodríguez‐Vico

et al. 2010

Chemistry & Biodiversity

121

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Interest in D-amino acids has increased in recent decades with the development of new analytical methods highlighting their presence in all kingdoms of life. Their involvement in physiological functions, and the presence of metabolic routes for their synthesis and degradation have been shown. Furthermore, D-amino acids are gaining considerable importance in the pharmaceutical industry. The immense amount of information scattered throughout the literature makes it difficult to achieve a general overview of their applications. This review summarizes the state-of-the-art on D-amino acid applications and occurrence, providing both established and neophyte researchers with a comprehensive introduction to this topic.

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