×

Fluorogenic peptides for the detection of protease activity

  • US 6,037,137 A
  • Filed: 02/20/1997
  • Issued: 03/14/2000
  • Est. Priority Date: 02/20/1997
  • Status: Expired due to Term
First Claim
Patent Images

1. A fluorogenic composition for the detection of the activity of a protease, said composition having the formula:

  • ##STR19## wherein, P is a peptide comprising a protease binding site for said protease, said binding site consisting of about 2 to about 8 amino acids;

    F1 and F2 are fluorophores and F1 is attached to the amino terminal amino acid and F2 is attached to the carboxyl terminal amino acid;

    S1 and S2, when present, are peptide spacers ranging in length from 1 to about 50 amino acids and S1, when present, is attached to the amino terminal amino acid and S2, when present, is attached to the carboxyl terminal amino acid;

    i, j, k, 1, m, n, o, p, q, and r are independently 0 or 1;

    aa1 and aa10 are independently selected from the group consisting of lysine, ornithine and cysteine;

    aa2, aa3, aa8, and aa9 are independently selected from the group consisting of Asp, Glu, Lys, Ornithine, Arg, Citulline, homocitrulline, Ser, homoserine, Thr, and Tyr;

    aa5, aa4, aa6, and aa7 are independently selected from the group consisting of proline, 3,4-dehydroproline, hydroxyproline, alpha aminoisobutyric acid and N-methyl alanine;

    X is selected from the group consisting of Gly, β

    Ala, γ

    Abu ,Gly-Gly, Ahx, β

    Ala-Gly, β

    Ala-β

    Ala, γ

    Abu-Gly, β

    Ala-γ

    Abu, Gly-Gly-Gly (SEQ ID NO;

    37), γ

    Abu-γ

    Abu, Ahx-Gly, β

    Ala-Gly-Gly, Ahx-β

    Ala, β

    Ala-β

    Ala-Gly, Gly-Gly-Gly-Gly, Ahx-γ

    Abu, β

    Ala-β

    Ala-β

    Ala, γ

    Abu-β

    Ala-Gly, γ

    Abu-γ

    Abu-Gly, Ahx-Ahx, γ

    Abu-γ

    Abu-β

    Ala, and Ahx-Ahx-Gly;

    Y is selected from the group consisting of Gly, β

    Ala, γ

    Abu, Gly-Gly, Ahx, Gly-β

    Ala, β

    Ala-β

    Ala, Gly-γ

    Abu, γ

    Abu-β

    Ala, Gly-Gly-Gly, γ

    Abu-γ

    Abu, Gly-Ahx, Gly-Gly-β

    Ala,β

    Ala-Ahx, Gly-β

    Ala-β

    Ala, Gly-Gly-Gly-Gly (SEQ ID NO;

    37), γ

    Abu-Ahx, β

    Ala-β

    Ala-β

    Ala, Gly-β

    Ala-γ

    Abu, Gly-γ

    Abu-γ

    Abu, Ahx-Ahx, β

    Ala-γ

    Abu-γ

    Abu, and Gly-Ahx-Ahx;

    when i is 1, S1 is joined to aa1 by a peptide bond through a terminal alpha amino group of aa1 ; and

    when r is 1, S2 is joined to aa10 by a peptide bond through a terminal alpha carboxyl group of aa10.

View all claims
  • 1 Assignment
Timeline View
Assignment View
    ×
    ×