Bradykinin analogs as selective thrombin inhibitors

Details Bradykinin analogs as selective thrombin inhibitors Bradykinin analogs as selective thrombin inhibitors

A - Human Necessities

61

K

A61K 38/10 (2006.01) A61K 38/07 (2006.01) A61K 38/08 (2006.01) A61K 38/16 (2006.01) A61P 7/02 (2006.01) C07K 5/037 (2006.01) C07K 5/11 (2006.01) C07K 7/02 (2006.01) C07K 7/18 (2006.01) C07K 14/00 (2006.01)

Patent

CA 2221865

Thrombin-induced and ADP-induced platelet and other cell activation is inhibited without affecting thrombin's other proteolytic activity by administration of a bradykinin sequence related analogous peptide. Bradykinin analogs are peptides to which substitutions, additions or deletions have been made to the first four amino acids of the amino acid sequence of native bradykinin. The bradykinin analogs described inhibit .alpha.-thrombin-induced and ADP-induced platelet activation and secretion, inhibit a-thrombin-induced calcium mobilization, and prevent .alpha.-thrombin from cleaving its platelet receptor. The bradykinin analogs may comprise single- or multiple-chain peptides.

L'administration d'un peptide analogue lié à une séquence de brakykinine permet d'inhiber l'activation des plaquettes et des autres cellules induite par la thrombine et par l'adénosine diphosphate sans modifier l'autre activité protéolytique de la thrombine. Les analogues de la brakykinine sont des peptides qui ont subi des substitutions, des adjonctions ou des suppressions par rapport aux quatre premiers acides aminés de la séquence d'acides aminés de la bradykinine native. Les analogues de la bradykinine selon l'invention inhibent l'activation et la sécrétion des plaquettes induites par l' alpha -thrombine et l'adénosine diphosphate, et inhibent également la mobilisation du calcium induite par l' alpha -thrombine. Par ailleurs, ils empêchent l' alpha -thrombine de diviser son récepteur de plaquettes. Les analogues de la bradykinine peuvent comprendre des peptides à simples et à multiples chaînes.

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