Substituted phosphonic analogues of phenylglycine as inhibitors of phenylalanine ammonia lyase from potatoes

Wanat, Weronika; Talma, Michał; Hurek, J.; Pawełczak, Małgorzata; Kafarski, Paweł

doi:10.1016/j.biochi.2018.06.005

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…Aminobenzylphosphonic acids were available from previous studies [13] and were synthesized based on the procedure described by Oleksyszyn and Soroka [28,29,30]. All compounds used in this work were racemic mixtures in the form of crystalline solids and could safely be stored at room temperature for several months.…”

Section: Methodsmentioning

confidence: 99%

“…Having a series of phosphonic acid analogues of phenylglycine [13] variably substituted in aromatic rings in hand, we decided to determine their activity towards the commonly studied aminopeptidase N (alanine aminopeptidase, pAPN) from porcine kidney [11,14,15], which is a good model enzyme for human alanine aminopeptidase (hAPN), because the two enzymes contain one zinc ion in the active site and exhibit a similar pattern of activity towards series of the same synthetic substrates [16]. The human enzyme is overexpressed in various types of cancer and on the surface of the vasculature undergoing angiogenesis and is thus considered as a promising target for anticancer therapy [4,10,11,12,13,14,15,16,17]. The pattern of inhibitory activity found for pAPN was compared with the experimentally determined activity of the same set of compounds towards the newly isolated and only preliminarily characterized aminopeptidase from barley seeds [18,19].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2019

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…α‐Hydroxy phosphonates have attracted great attention as they are biologically active and valuable synthetic precursors for the synthesis of related organophosphonates such as α‐aminophosphonates, alkoxy‐ and acyloxy‐phosphonates, ketophosphonates and halophosphonates [4–9] . Moreover, bis‐α‐hydroxy phosphonates can be used as excellent candidates as diol monomers for the synthesis of phosphorus‐containing polymers with flame retardant properties [10–12] …”

Section: Introductionmentioning

confidence: 99%

Enzyme Inhibition Properties and Molecular Docking Studies of 4‐Sulfonate Containing Aryl α‐Hydroxyphosphonates Based Hybrid Molecules

Şahin

Bingöl

Onur

et al. 2022

Chemistry & Biodiversity

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In this study, a series of new hybrid molecules containing two important functional groups on the same skeleton were designed. 4‐Hydroxybenzaldehyde and its two different derivatives were converted into their respective sulphonates by interacting with tosylchloride and methanesulfonyl chloride. Then, the desired molecules were synthesized by adding diethoxyphosphonate to the aldehyde group. Also, novel synthesis of hybrid compounds (4a–c and 5a–c) were tested toward some metabolic enzymes like carbonic anhydrase I and II isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE) enzyme. The synthesis of hybrid compounds (4a–c and 5a–c) showed Ki values of in range of 25.084±4.73‐69.853±15.19 nM against hCA I, 32.325±1.67–82.761±22.73 nM against hCA II and 1.699±0.25 and 3.500±0.91 nM against AChE. For these compounds, compound 4c showed maximum inhibition effect against hCA I and hCA II isoenzymes and compound 5b showed maximum inhibition effect against AChE enzyme. By performing docking studies of the most active compounds for their binding modes and interactions were determined.

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“…It is well known that libraries of structurally related, low-molecular enzyme inhibitors are a good starting point for the design of more potent ones following analysis of their interactions with enzymes at molecular level [13]. Quite frequently molecular modeling is of use as a tool in such studies.…”

Section: Introductionmentioning

confidence: 99%

“…Having in hand a series of phosphonic analogues of phenylglycine [12], variably substituted in aromatic ring we decided to compare their activity towards commonly studied aminopeptidase N (alanine aminopeptidase, pAPN) from porcine kidney [11,14,15], a model enzyme for human one. Human enzyme is overexpressed in various types of cancer and on the surface of vasculature undergoing angiogenesis and thus being considered as a promising target for anticancer therapy [4,[10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Phosphonic Analogues of Phenylglycine as Inhibitors of Aminopeptidases: Comparison of Porcine Aminopeptidase N, Bovine Leucine Aminopeptidase and Aminopeptidase from Barley Seeds

Wanat¹,

Talma²,

Pawełczak³

et al. 2019

Preprint

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Inhibitory activity of 14 phosphonic analogues of phenylglycine, substituted in aromatic ring by fluorine and chlorine, was determined towards porcine aminopeptidase N. The obtained data served as a basis for studying their interaction with the enzyme as modelled by the use of Schrödinger Release 2018 program. The observed linearity between modelled Gibbs free energy differences and inhibitory constants indicated the usefulness of this program. The obtained binding mode was compared with this modelled for bovine lens leucine aminopeptidase. Although both enzymes differ in the number of zinc ions present in the active site, they are considered to exhibit similar activity towards substrates and inhibitors. Our studies seem to support that  supposition since the modes of binding of the studied inhibitors are quite similar. Additionally, inhibitory activity of the phosphonic analogues of phenylglycine towards barley aminopetpidase was determined showing that this enzyme could be considered as neutral aminopeptidase.

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Substituted phosphonic analogues of phenylglycine as inhibitors of phenylalanine ammonia lyase from potatoes

Cited by 7 publications

References 36 publications

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

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

Enzyme Inhibition Properties and Molecular Docking Studies of 4‐Sulfonate Containing Aryl α‐Hydroxyphosphonates Based Hybrid Molecules

Phosphonic Analogues of Phenylglycine as Inhibitors of Aminopeptidases: Comparison of Porcine Aminopeptidase N, Bovine Leucine Aminopeptidase and Aminopeptidase from Barley Seeds

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