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Keywords = phenylglycine analogues

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10 pages, 1877 KiB  
Article
A Chirality Chain in Phenylglycine, Phenylpropionic Acid, and Ibuprofen
by Henri Brunner, Takashi Tsuno and Gábor Balázs
Symmetry 2021, 13(1), 55; https://doi.org/10.3390/sym13010055 - 31 Dec 2020
Cited by 5 | Viewed by 2909
Abstract
Our strategy to analyze the structures of natural amino acids with respect to the interaction of three different elements of chirality within the molecules was applied to the non-natural amino acid (S)-α-phenylglycine, its analogue (S)-α-phenylpropionic acid, and the drug [...] Read more.
Our strategy to analyze the structures of natural amino acids with respect to the interaction of three different elements of chirality within the molecules was applied to the non-natural amino acid (S)-α-phenylglycine, its analogue (S)-α-phenylpropionic acid, and the drug (S)-ibuprofen. The three chirality elements are the configuration at Cα, the conformation at the Cα-C’ bond, and the distortion of the planar carboxylic group to a flat asymmetric tetrahedron. In all three compounds, a given (S) configuration at Cα predominantly induces (M) conformation at the Cα-C’ bond, which in turn preferentially distorts the carboxylic group to a tetrahedron with (R) configuration. Both steps of this chirality chain display high selectivities. Due to varying co-crystallization partners, in all the structures the molecules are in different environments with respect to packing and hydrogen bonding. Nevertheless, the structural pattern and the diaselectivities of the chirality chain persist. For phenylglycine, DFT (Density Functional Theory) calculations confirm the structural results. Full article
(This article belongs to the Special Issue A Symmetry Breaking in Design and Production of Enantiomeric Drugs)
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12 pages, 5926 KiB  
Article
Phosphonic Acid Analogues of Phenylglycine as Inhibitors of Aminopeptidases: Comparison of Porcine Aminopeptidase N, Bovine Leucine Aminopeptidase, Tomato Acidic Leucine Aminopeptidase and Aminopeptidase from Barley Seeds
by Weronika Wanat, Michał Talma, Małgorzata Pawełczak and Paweł Kafarski
Pharmaceuticals 2019, 12(3), 139; https://doi.org/10.3390/ph12030139 - 17 Sep 2019
Cited by 8 | Viewed by 4699
Abstract
The inhibitory activity of 14 racemic phosphonic acid analogs of phenylglycine, substituted in aromatic rings, towards porcine aminopeptidase N (pAPN) and barley seed aminopeptidase was determined experimentally. The obtained patterns of the inhibitory activity against the two enzymes were similar. The obtained data [...] Read more.
The inhibitory activity of 14 racemic phosphonic acid analogs of phenylglycine, substituted in aromatic rings, towards porcine aminopeptidase N (pAPN) and barley seed aminopeptidase was determined experimentally. The obtained patterns of the inhibitory activity against the two enzymes were similar. The obtained data served as a basis for studying the binding modes of these inhibitors by pAPN using molecular modeling. It was found that their aminophosphonate fragments were bound in a highly uniform manner and that the difference in their affinities most likely resulted from the mode of substitution of their phenyl rings. The obtained binding modes towards pAPN were compared, with these predicted for bovine lens leucine aminopeptidase (blLAP) and tomato acidic leucine aminopeptidase (tLAPA). The performed studies indicated that the binding manner of the phenylglycine analogs to biLAP and tLAPA are significantly similar and differ slightly from that predicted for pAPN. Full article
(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs)
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