Effect of staphylokinase-derived nonadecapeptide on the activation of plasminogen.
Staphylokinase (SAK) expresses plasminogen activator (PA) activity by forming a complex with plasmin. The interaction between the plasmin-SAK complex and plasminogen was investigated using synthesized peptides, which were constructed according to the amino acid sequence of the SAK molecule. A synthetic nonadecapeptide (SAK22-40) corresponding to Glu22-Leu40 by the SAK molecule enhanced the activation of Glu-plasminogen by the plasmin-SAK complex. Analysis of IAsys resonant mirror biosensor showed that SAK22-40 bound to Glu-plasminogen. This binding was completely inhibited by IgG against the B-chain in the plasminogen molecule. But, this binding was not inhibited by IgG against lysine-binding sites (LBS) of the A-chain in the plasminogen molecule. The substitution of Lys35 with Ala in SAK22-40 did not enhance the activation of Glu-plasminogen by the plasmin-SAK complex. When SAK22-40 was administrated in a mouse thrombosis model, earlier recanalization was observed than in mice with vehicle administration. Thus, a newly synthesized peptide, SAK22-40 enhanced Glu-plasminogen activation and induced effective thrombolysis.
Okada
Kiyotaka
K
Department of Physiology, Kinki University School of Medicine, Ohnohigashi 377-2, Osakasayama City, Osaka, 589-8511, Japan.
Ueshima
Shigeru
S
Matsuno
Hiroyuki
H
Kawao
Naoyuki
N
Okamoto
Chikako
C
Tanaka
Masaki
M
Matsuo
Osamu
O
D000818:Animals; D001665:Binding Sites; D015374:Biosensing Techniques; D002341:Carotid Artery Thrombosis / Q000188:drug therapy; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D015912:Thrombolytic Therapy
D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D010958:Plasminogen; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus