Multi-Target Anticoagulant Regulation by Peptides from Medicinal Leeches: A Unique Natural Strategy against...

Thrombotic diseases remain a major global health burden. Current anticoagulants are often limited by bleeding risks and narrow therapeutic windows, largely due to their single-target mechanisms. In contrast, medicinal leeches secrete diverse peptides that naturally and synergistically modulate multiple steps of the hemostatic system.

This paper systematically reviews published biochemical, structural, functional, and omics studies on leech-derived anticoagulant peptides, classifying them according to their molecular targets and antithrombotic mechanisms.

Leech-derived peptides act synergistically at multiple key points of the coagulation cascade: (1) they inhibit platelet adhesion and aggregation by blocking the vWF-collagen interaction or suppressing GPIIb/IIIa; (2) they directly inhibit core coagulation proteases, such as thrombin and factor Xa; and (3) they interfere with fibrin stabilization and promote its dissolution by inhibiting factor XIIIa or modulating the fibrinolytic and intrinsic protease systems. From a molecular perspective, multispecies omics analyses have revealed a significant expansion of antithrombotic gene families and identified numerous novel peptide candidate genes.

Leech-derived peptides provide a unique natural platform for multi-target anticoagulation and represent promising leads for next-generation antithrombotic agents. Combining traditional purification with genomics-guided discovery will accelerate mechanism elucidation, structural optimization, and translational development.