American Society of Hirudotherapy

Hirudin or hirudin-like factor - that is the question: insights from the analyses of natural and synthetic HLF variants

Research article published in FEBS letters (2020)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportDrug DevelopmentClinical TrialsGenomics & ProteomicsMüller C et al. · FEBS letters, 2020

Abstract

The hirudin-like factor 1 (HLF1) of Hirudo medicinalis belongs to a new class of leech-derived factors. In previous investigations, HLF1 did not exhibit anticoagulatory activities. Here, we describe the analysis of natural and synthetic variants of HLF1 and HLF-Hyb, a yet uncharacterized member of the HLF family. Modifications within the N terminus of HLF1 have a strong impact on its activity. Some variants of HLF1 exhibit thrombin-inhibiting activity comparable to hirudins, whereas others have reduced or no activity. The analyses of HLF-Hyb variants revealed a strong impact of the central globular domain on activity. Our results indicate a comparable mode of action of hirudins and thrombin-inhibiting HLF variants. Finally, we propose and discuss criteria for classifying hirudins and HLFs.

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

Publication typeJournal Article
Indexed MeSH termsAnimalsHirudinsHumansLeechesMutagenesis, Site-DirectedProtein DomainsProtein EngineeringSalivaThrombin

Summary

The hirudin-like factor 1 (HLF1) of Hirudo medicinalis belongs to a new class of leech-derived factors. In previous investigations, HLF1 did not exhibit anticoagulatory activities.

Why This Matters for Hirudotherapy

This study analyzed natural and synthetic variants of hirudin-like factor 1 (HLF1) and the previously uncharacterized HLF-Hyb from Hirudo medicinalis, examining how modifications in the N terminus and central globular domain affect thrombin-inhibiting activity. These findings are directly relevant to the leech salivary secretome, as they identify structural determinants that distinguish functional hirudins from hirudin-like factors, demonstrate that certain HLF variants can achieve thrombin inhibition comparable to hirudins, and propose criteria for classifying these leech-derived protein families. Such molecular-level understanding of salivary anticoagulants contributes to the mechanistic foundation underlying hirudotherapy. However, this work focuses on characterizing isolated protein variants and does not involve whole-leech saliva, clinical application, or therapeutic outcomes; its relevance to applied hirudotherapy is limited to providing structural and functional insights about specific salivary components.

Citation

Hirudin or hirudin-like factor - that is the question: insights from the analyses of natural and synthetic HLF variants.

Müller C et al. · FEBS letters, 2020

DOI

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