An intramolecularly quenched fluorescent tripeptide as a fluorogenic substrate of angiotensin-I-converting enzyme and of bacterial dipeptidyl carboxypeptidase

Eur J Biochem. 1978 Jun 15;87(2):265-73. doi: 10.1111/j.1432-1033.1978.tb12375.x.

Abstract

The N-acyltripeptide 2-aminobenzoylglycyl-p-nitrophenylalanylproline was synthesized and applied as a substrate in the assay of angiotensin-I-converting enzyme from calf lung and human serum, and of the bacterial dipeptidyl carboxypeptidase from Escherichia coli. This compound belongs to a new class of substrates for proteolytic enzymes, having the general structure F--X--Q in which fluorescence of group F is quenched by intramolecular interaction with the group Q. Enzymatic cleavage of the peptide chain (X stands for one or more amino acid residues) generates the unquenched F-containing derivative and the resulting fluorescence is used for quantitative measurement of the hydrolysis rate. Cleavage of the Gly-Phe(NO2) peptide bond in the weakly fluorescent 2-amino-benzoylglycyl-p-nitrophenylalanylproline molecule results in appearance of the 71 times higher fluorescence (lambdamax = 415 nm) of 2-aminobenzoylglycine. Continuous recording of the rising fluorescence allows convenient, sensitive and specific determination of the enzymatic activity, applicable to crude enzyme preparations and human serum. The activity of the mammalian enzyme, measured by this method, is enhanced by Cl- ions and inhibited by low concentrations of EDTA and [Asn1, Val5]angiotensin II. Kinetic measurements showed Michaelis-Menten behavior, Km = 0.21 +/- 0.1 mM and 0.16 +/- 0.1 mM for the calf lung and the bacterial enzyme respectively.

MeSH terms

  • Carboxypeptidases / metabolism*
  • Chlorides / pharmacology
  • Dipeptides
  • Enzyme Activation
  • Escherichia coli / enzymology
  • Fluorescent Dyes*
  • Humans
  • Kinetics
  • Oligopeptides*
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / metabolism*
  • Spectrophotometry

Substances

  • Chlorides
  • Dipeptides
  • Fluorescent Dyes
  • Oligopeptides
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A