Studies on the anticoagulant, antimetastatic and heparin-binding properties of ghilanten-related inhibitors

The purpose of this study was to investigate the structure-activity relationships of ghilanten, an anticoagulant-antimetastatic protein of the South American leech Haementeria ghilianii. Five sequence-related variants of ghilanten, termed P1-P5, were purified and were shown to potently block the active-site hydrolysis of methoxycarbonyl-D-cyclohexylglycyl-glycyl-arginine-p-nitroanilide acetate by the human blood coagulation enzyme factor Xa; inhibition was rapid and stoichiometric. The amino acid sequence of P5 revealed a consensus sequence for heparin-binding at the carboxy-terminus. A synthetic peptide homologous to this region (93P-N-G-L-K-R-D-K-L-G-C-E-Y-C-E-C-R-P-K-R-K-L-I-P-R-L-S119) bound 125I-labelled heparin maximally at physiological pH and salt concentration. When administered intravenously to mice, the peptide suppressed lung metastases although less potentially than whole ghilanten. These findings suggest that the carboxy-terminal heparin-binding region may play a role in the antimetastatic action of the inhibitor.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Five variants of ghilanten, an anticoagulant-antimetastatic protein from the leech Haementeria ghilianii, potently and stoichiometrically block factor Xa active-site hydrolysis; a synthetic peptide from its heparin-binding carboxy-terminal region also suppressed mouse lung metastases, suggesting this region may contribute to the antimetastatic action.

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