Ab Kabi

Kabi Ab

Kabivitrum Ab

Leif R Simonsson

Karl G Claeson

Leif E Aurell

Salo Arielly

Peptide sequences consisting of 2-4 amino acids with high affinity and comparatively high specificity to a number of various, physiologically important proteases are known to have been synthetized before. Such sequences with an added C-terminal marker have been widely used as substrates for the quantitative determination of the kind of proteases mentioned above. The method is based on the fact that the marker is split off under influence of the enzyme and that the liberated marker possesses an easily measurable, for instance, optic property which differs from that of the original substrate. The type of markers used until today have mainly been chromophores or fluorophores which can be quantified by photometry or fluorometry. The present invention relates to a new type of markers coupled to known peptide sequences. These markers are luminol or isoluminol which in their free state can be brought to luminate intensely, but lose considerably in luminescence when they are amide-bound to a peptide sequence. The peptide derivatives consist of acyl derivates of luminol (5-amino-2,3-dihydro-1,4-phthalazinedione) or isoluminol (6-amino-2,3-dihydro-1,4-phthalazinedione) where the acyl residue consists of an amide-bound amino acid or amino acid sequence with 2-4 amino acid residues and where the .alpha.-amino group is either free of acylated. The greatest advantages of the luminogenic substrates according to the invention are that they

Peptide substrates for determination of protease activity

Easily split enzyme substrates for the quantification of proteases having the general formula

Easily split substrates for the quantification of proteases

Serine proteases in a substance such as blood are determined by contacting the substance with a novel chromogenic or fluorgenic substrate for serine proteinases and spectrophotometrically measuring the quantity of a chromophore or fluorescent compound released from the substrate by serine proteases in the substance. The novel substrate has the amino acid sequence-ILe-A-Gly-Arg-wherein A is Asp or Glu substituted in the carboxylic group by esterification or amidation. The novel substrate increases sensitivity and accuracy of the determination.

Determination of serine proteases

Bradykinin-inhibiting tripeptide derivatives

Chromogenic or fluorogenic enzyme substrates for serine proteases containing the amino acid sequence Ile-A-Gly-Arg wherein A is Asp or Glu substituted in the carboxylic group by esterification or amidation, a method of preparation thereof, and use thereof.

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Hisings-Backa, Sweden

Leif R Simonsson