Treatment of shock, e.g. due to bacterial toxins or hemorrhagic shock associated with viral infections, comprises using peptides matching the inducible VE-cadherin binding moiety of human fibrin Bbeta-chain

摘要

The use of peptides (I), which match the inducible VE-cadherin binding moiety of the Bbeta -chain of human fibrin (i.e. Bbeta 15-42), for the treatment of shock, is new, where (I) have a specific structure based on a glycyl-(histidyl or prolyl)-argininyl N-terminus and/or have a specific N-terminal sequence of 28 amino acids. The use of peptides (I), which match the inducible VE-cadherin binding moiety of the Bbeta -chain of human fibrin (i.e. Bbeta 15-42), is claimed for the production of a pharmaceutical preparation for the treatment of shock, where (I) are of formula R 1R 2N-CH 2-C(O)-Z 1-Z 2 (I') and/or have the N-terminal amino acid sequence Gly-His-Arg-Pro-Leu-Asp-Lys-Lys-Arg-Glu-Glu-Ala-Pro-Ser-Leu-Arg-Pro-Ala-Pro-Pro-Pro-Ile-Ser-Gly-Gly-Gly-Tyr-Arg (I''). R 1, R 2H or saturated or unsaturated 1-10C (preferably 1-3C) hydrocarbyl; Z 1histidine or proline residue; Z 2arginine residue or a peptide or protein residue (preferably of 2-30 amino acids) with an initial arginine residue. ACTIVITY : Vasotropic; Antibacterial; Immunosuppressive; Virucide. In tests in mice with dengue viruses associated shock, the degree of mortality in a group treated with Gly-His-Arg-Pro-Leu-Asp-Lys-Lys-Arg-Glu-Glu-Ala-Pro-Ser-Leu-Arg-Pro-Ala-Pro-Pro-Pro-Ile-Ser-Gly-Gly-Gly-Tyr-Arg (Ia) (Bbeta 15-42) at 4800 mu g/kg i.p. twice daily from day 3 to day 8 after infection was 0%, compared with 40% in an untreated control group. MECHANISM OF ACTION : Human fibrin Bbeta -chain inducible VE-cadherin binding moiety mimetic.