Enzyme inhibitory activity of certain phosphonate esters against chymotrypsin, trypsin and acetylcholinesterase

Boone, Betty J.; Becker, Elmer L.; Canham, Donald H.

doi:10.1016/0926-6569(64)90308-6

Cited by 8 publications

(14 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The minimum in inhibition of trypsin given by the 6-chloro-hexyl phosphonate might be due to the repulsion of the electron-rich chloro group by the putative anionic site (15). By the same reasoning, the minimum in the inhibition of C'I given by the 5-chloropentyl phosphonate could be due to the possession of a similar anionic group.…”

Section: Discussionmentioning

confidence: 88%

“…The low ionic strength prevented dissociation of C'la from the cell during the reaction (17), and pH 8.0 was used in order for the results to be directly comparable with previous work on other enzymes (7,15).…”

Section: Methodsmentioning

confidence: 89%

“…Phosphonate Inhibitors.--The p-nitrophenylethyl alkyl, phenyl alkyl, and the ¢o-chloroalkyl phosphonates have been described previously (7,14,15). The synthesis and properties of p-nitrophenylethy160-aminoalkyl phosphonates will be described subsequently by Mr. Robert Stat~, Mr. Dennis Werber, and Mr. Gim Tijoe of American University.…”

Section: Methodsmentioning

confidence: 99%

“…2, C) on the inhibition of C'la. For comparison, the inhibitory activity of these same compounds against "true" acetylcholinesterase, trypsin, and chymotrypsin reported previously (7,15) is also plotted. The inhibition pattern for acetylcholinesterase differs completely from any of the other enzymes.…”

Section: Inhibition Of Whole Complement By Phosphonatementioning

confidence: 99%

See 3 more Smart Citations

A Comparison of the Specificity of Inhibition by Phosphonate Esters of the First Component of Complement and the Antigen-Induced Release of Histamine From Guinea Pig Lung

Becker

Austen

1964

The Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

The ability of a number p-nitrophenylethyl alkyl, phenyl alkyl, chloroalkyl, and aminoalkyl phosphonates to inhibit the activated first component (C'1a) of guinea pig complement, and the antigen-induced release of histamine from sliced, perfused guinea pig lung has been compared. C'1a in its reactivity with these phosphonates is distinctly more similar to trypsin than to any of the other enzymes studied previously. It is suggested that both trypsin and C'1a possess an anionic group in the active center of the respective enzyme, but the distance between the anionic and esteratic site in C'1a might be less than in trypsin. The pattern of inhibition of histamine relase by the alkyl, phenyl alkyl, and chloroalkyl phosphonates is similar to the inhibition of C'1a by these compounds, although distinct differences are apparent. The aminoalkyl phosphonates are distinctly less active inhibitors of histamine release than the corresponding alkyl phosphonates, whereas the reverse is true of the inhibition of C'1a. On the basis of these differences, it is tentatively concluded that the organophosphorus-inhibitable enzymes in the guinea pig systems studied here are similar but not identical.

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Inhibition Of Whole Complement By Phosphonatementioning

confidence: 99%

See 2 more Smart Citations

A Comparison of the Specificity of Inhibition by Phosphonate Esters of the First Component of Complement and the Antigen-Induced Release of Histamine From Guinea Pig Lung

Becker

Austen

1964

The Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Their inhibitory activity varies in the different homologous series with changes in structure of the R group to give the so called "inhibition profiles." These inhibition profiles are characteristic for and specific to such well-defined esterases as trypsin, chyinotrypsin, acetylcholinesterase, and Crla (2,3), as well as the esterases involved in the antigen-induced release of histamine from sensitized slices of guinea pig lung and from rat peritoneal mast cells sensitized with rat homocytotropic antibody or with rabbit anti-rat gamma globulin (reviewed in reference 4).…”

mentioning

confidence: 99%

ESTERASES OF THE POLYMORPHONUCLEAR LEUKOCYTE CAPABLE OF HYDROLYZING ACETYL DL-PHENYL-ALANINE ß-NAPHTHYL ESTER

Becker

Ward

1969

The Journal of Experimental Medicine

Self Cite

View full text Add to dashboard Cite

Previous published work has led to the hypothesis that the activatable esterase of chemotaxis is a serine esterase of the rabbit polymorphonuclear leukocyte existing in an inert, phosphonate insusceptible form, which after activation is capable of hydrolyzing aromatic amino acid esters and being inhibited by phosphonates. In the present study, directed to the testing of this hypothesis, we have shown that rabbit peritoneal polymorphonuclear leukocytes contain three esterases capable of hydrolyzing the aromatic amino acid ester, acetyl DL-phenylalanine ß-naphthyl ester. Two of these esterases, esterase 1 and esterase 2, are inhibited by various p-nitrophenyl ethyl phosphonate esters. The inhibition of each esterase is irreversible and progressive with time. When the logarithm of the esterase activity remaining after cell and inhibitor have been in contact for a constant time is plotted against the concentration of inhibitor, a straight line results. These results support the conclusion that both esterases are serine esterases. The third esterase, esterase 3, differs from the other two by its inability to be inactivated by any of the phosphonates no matter how high the concentration of phosphonate or prolonged the period of incubation of cell with phosphonate. The activity of esterase 1 is at least 10,000 times more easily inhibited by phosphonates than is that of esterase 2; incubating rabbit polymorphonuclear leukocytes for 15 min at 27°C with 10–9–10–8 M concentrations of various phosphonates inactivates esterase 1, but it required 10–6–10–4 M concentrations of the same phosphonates to inhibit esterase 2. The inhibition profiles of esterase 1 are distinctly different from those of esterase 2 when the two esterases are tested with the phenylalkylphosphonates, chloroalkylphosphonates, and alkylphosphonates. The inhibition profile of esterase 1 is essentially the same as that of the activatable esterase of chemotaxis obtained previously when the same three homologous series of phosphonates were tested for their ability to protect against deactivation by the chemotactic factor or give chemotactic-dependent inhibition. It is tentatively concluded that esterase 1 of the rabbit peritoneal neutrophil is the activated form of the activatable esterase of chemotaxis.

show abstract

Interplay among Enzyme Mechanism, Protein Structure, and the Design of Serine Protease Inhibitors

Bartlett

Sampson

Reich

et al. 1990

Use of X-Ray Crystallography in the Design of Antiviral Agents

View full text Add to dashboard Cite

Enzyme inhibitory activity of certain phosphonate esters against chymotrypsin, trypsin and acetylcholinesterase

Cited by 8 publications

References 4 publications

A Comparison of the Specificity of Inhibition by Phosphonate Esters of the First Component of Complement and the Antigen-Induced Release of Histamine From Guinea Pig Lung

A Comparison of the Specificity of Inhibition by Phosphonate Esters of the First Component of Complement and the Antigen-Induced Release of Histamine From Guinea Pig Lung

ESTERASES OF THE POLYMORPHONUCLEAR LEUKOCYTE CAPABLE OF HYDROLYZING ACETYL DL-PHENYL-ALANINE ß-NAPHTHYL ESTER

Interplay among Enzyme Mechanism, Protein Structure, and the Design of Serine Protease Inhibitors

Contact Info

Product

Resources

About