Skip to main content
Journal cover image

p-Amidino esters as irreversible inhibitors of factors IXa and Xa and thrombin.

Publication ,  Journal Article
Turner, AD; Monroe, DM; Roberts, HR; Porter, NA; Pizzo, SV
Published in: Biochemistry
August 26, 1986

A number of inhibitors of thrombin and factor Xa have been described; however, only one inhibitor of factor IXa has been reported. This compound, dansyl-Glu-Gly-Arg chloromethyl ketone (DEGER), inhibits porcine factor IXa with a second-order rate constant of 2.2 X 10(4) M-1 min-1. We now describe the synthesis and characterization of three p-amidinophenyl esters that inhibit human factor IXa with second-order rate constants comparable to those observed with human and bovine factor Xa and alpha-thrombin. These rate constants of inhibition, moreover, are 2-30-fold greater than observed when DEGER is employed to inhibit porcine factor IXa. Additional advantages of these derivatives include their ease of synthesis and low degree of toxicity. The p-amidinophenyl ester of benzoic acid was employed to inhibit human factor IXa, and the plasma clearance of the protein was studied in mice. These experiments demonstrate for the first time that the endothelial binding previously reported with factor IXa is independent of the active site, a finding similar to the behavior observed with factor Xa and alpha-thrombin in this and previous reports.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

August 26, 1986

Volume

25

Issue

17

Start / End Page

4929 / 4935

Location

United States

Related Subject Headings

  • Thrombin
  • Structure-Activity Relationship
  • Protein Binding
  • Magnetic Resonance Spectroscopy
  • Kinetics
  • Indicators and Reagents
  • Humans
  • Factor Xa
  • Factor X
  • Factor IXa
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Turner, A. D., Monroe, D. M., Roberts, H. R., Porter, N. A., & Pizzo, S. V. (1986). p-Amidino esters as irreversible inhibitors of factors IXa and Xa and thrombin. Biochemistry, 25(17), 4929–4935. https://doi.org/10.1021/bi00365a031
Turner, A. D., D. M. Monroe, H. R. Roberts, N. A. Porter, and S. V. Pizzo. “p-Amidino esters as irreversible inhibitors of factors IXa and Xa and thrombin.Biochemistry 25, no. 17 (August 26, 1986): 4929–35. https://doi.org/10.1021/bi00365a031.
Turner AD, Monroe DM, Roberts HR, Porter NA, Pizzo SV. p-Amidino esters as irreversible inhibitors of factors IXa and Xa and thrombin. Biochemistry. 1986 Aug 26;25(17):4929–35.
Turner, A. D., et al. “p-Amidino esters as irreversible inhibitors of factors IXa and Xa and thrombin.Biochemistry, vol. 25, no. 17, Aug. 1986, pp. 4929–35. Pubmed, doi:10.1021/bi00365a031.
Turner AD, Monroe DM, Roberts HR, Porter NA, Pizzo SV. p-Amidino esters as irreversible inhibitors of factors IXa and Xa and thrombin. Biochemistry. 1986 Aug 26;25(17):4929–4935.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

August 26, 1986

Volume

25

Issue

17

Start / End Page

4929 / 4935

Location

United States

Related Subject Headings

  • Thrombin
  • Structure-Activity Relationship
  • Protein Binding
  • Magnetic Resonance Spectroscopy
  • Kinetics
  • Indicators and Reagents
  • Humans
  • Factor Xa
  • Factor X
  • Factor IXa