American Society of Hirudotherapy

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

Comparative study published in Blood Coagul Fibrinolysis (1991)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Observational studySalivary PharmacologyDrug DevelopmentBrankamp RG et al. · Blood Coagul Fibrinolysis, 1991

Abstract

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.

Publication typeComparative StudyJournal Article
Indexed MeSH termsAmino Acid SequenceAnimalsAntineoplastic AgentsBinding SitesBlood ProteinsConsensus SequenceDrug SynergismFactor XaFactor Xa InhibitorsHeparinHumansInvertebrate Hormones

Summary

Ghilanten variants P1-P5 from Haementeria ghilianii potently block active-site hydrolysis by factor Xa; the carboxy-terminal heparin-binding region may play a role in antimetastatic action.

Why This Matters for Hirudotherapy

This comparative study investigated structure-activity relationships of ghilanten, an anticoagulant-antimetastatic protein from the South American leech Haementeria ghilianii, by purifying five sequence-related variants (P1–P5) and characterizing their factor Xa inhibition, heparin-binding properties, and antimetastatic activity. All variants potently and stoichiometrically blocked factor Xa active-site hydrolysis; the P5 carboxy-terminus contained a heparin-binding consensus sequence whose synthetic peptide homolog bound radiolabeled heparin at physiological conditions and suppressed lung metastases in mice when administered intravenously, though less effectively than whole ghilanten. For ASH, this is relevant as it concerns a leech-derived anticoagulant with additional antimetastatic properties and structure-function characterization. Caveat: This is a preclinical study using in vitro enzymology and a mouse metastasis model; no clinical data are presented and the leech species differs from Hirudo medicinalis.

Citation

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

Brankamp RG et al. · Blood Coagul Fibrinolysis, 1991

DOI

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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