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Ornithine Aminotransferase versus GABA Aminotransferase: Implications for the Design of New Anticancer Drugs
TLDR
In this review the two enzymes are compared with respect to their active‐site structures, catalytic and inactivation mechanisms, and selective inhibitors and insight is offered that could aid in the design and development of new selective inhibitors of OAT for the treatment of cancer. Expand
Design and Mechanism of (S)-3-Amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic Acid, a Highly Potent γ-Aminobutyric Acid Aminotransferase Inactivator for the Treatment of Addiction.
TLDR
In vivo studies in freely moving rats showed that 5 was dramatically superior to CPP-115 in suppressing the release of dopamine in the corpus striatum, which occurs subsequent to either an acute cocaine or nicotine challenge. Expand
PLP and GABA trigger GabR-mediated transcription regulation in Bacillus subtilis via external aldimine formation
TLDR
Results of in vitro and in vivo assays support the conclusion that AFPA is an agonistic ligand capable of triggering GabR-mediated transcription activation via formation of an external aldimine with PLP. Expand
Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands.
TLDR
The structure of (S,S)-9b, which showed the highest affinity of the series, is designed and synthesized and an optimal binding conformation is proposed, making it the most selective 5-HT(2A) receptor agonist ligand currently known. Expand
Mapping the Catechol Binding Site in Dopamine D1 Receptors: Synthesis and Evaluation of Two Parallel Series of Bicyclic Dopamine Analogues
TLDR
This work synthesized a parallel series of chroman compounds and showed that repositioning the oxygen atom in the heterocyclic ring decreases potency and confers D2‐like receptor selectivity to these compounds. Expand
Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (1S,3S)-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115)
TLDR
A novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5′-phosphate (PMP). Expand
Probing the steric requirements of the γ-aminobutyric acid aminotransferase active site with fluorinated analogues of vigabatrin.
TLDR
It is proposed that the GABA-AT active site has an accessory binding pocket that accommodates the vinyl group of vigabatrin and the fluoromethyl group of AFPA, but is too narrow to support the extra width of the distal methyl group in the synthesized analogues. Expand
Two continuous coupled assays for ornithine-δ-aminotransferase.
We have developed two new continuous coupled assays for ornithine-δ-aminotransferase (OAT) that are more sensitive than previous methods, measure activity in real time, and can be carried out inExpand
Probing the steric space at the floor of the D1 dopamine receptor orthosteric binding domain: 7α-, 7β-, 8α-, and 8β-methyl substituted dihydrexidine analogues.
TLDR
To probe the space at the floor of the orthosteric ligand binding site in the dopamine D(1) receptor, four methylated analogues of dihydrexidine were synthesized with substitutions at the 7 and 8 positions, showing losses in affinity when compared to DHX. Expand
Analogues of doxanthrine reveal differences between the dopamine D1 receptor binding properties of chromanoisoquinolines and hexahydrobenzo[a]phenanthridines.
TLDR
It is proposed, based on the biological results and molecular modeling studies, that slight conformational differences between the tetralin and chroman-based compounds lead to a shift in the location of the pendant ring substituents within the receptor. Expand
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