Tsetse fly protein provides anti-clotting agent with its own on-off switch

May 02, 2024

The antidote PNA (peptide nucleic acid) dissociates the two molecules, which ‘switches off’ the anti-clotting action of the combined molecule. The blue molecule is the peptide fragment derived from the tsetse fly, the red is the active site binder with the ketobenzothiazole fragment. The result could lead to new surgical and post-operative drugs that minimise the risk of serious bleeding. The anticoagulant combines a short protein molecule (a peptide) from a tsetse fly – a blood-feeding insect – with a second, synthesised peptide. The bonds holding the two peptides together can be broken on demand, providing the anticoagulant ingredient with its own on-off switch.

The image illustrates the combined action of two peptide molecules cooperating to inhibit thrombin.  The antidote PNA (peptide nucleic acid) dissociates the two molecules, which ‘switches off’ the anti-clotting action of the combined molecule.

The blue molecule is the peptide fragment derived from the tsetse fly, the red is the active site binder with the ketobenzothiazole fragment. They are ‘joined’ by PNA, non-convalent bonding. Source: University of Geneva

Researchers at the University of Sydney and University of Geneva have developed a new anticoagulant, whose anticlotting action can be rapidly stopped ‘on demand’. The result could lead to new surgical and post-operative drugs that minimise the risk of serious bleeding.

The research team applied a completely new method to discover the molecule. The anticoagulant combines a short protein molecule (a peptide) from a tsetse fly – a blood-feeding insect – with a second, synthesised peptide. The bonds holding the two peptides together can be broken on demand, providing the anticoagulant ingredient with its own on-off switch.

This new drug-discovery approach is a potential game-changer in surgery and for suppressing blood clots. It could also be applied in other fields such as immunotherapy.

The results are published today in Nature Biotechnology.

In addition to surgical applications, anticoagulant therapies are essential for managing a wide range of conditions, such as heart disease, stroke and venous thrombosis. However, current treatment options, such as heparin and warfarin, have major drawbacks, including the need for regular monitoring of blood coagulation and the risk of serious bleeding in the event of overdose.

About 15 percent of emergency hospital admissions due to adverse drug reactions are attributable to complications from anticoagulant treatments, emphasising the importance of developing new, safer and more effective therapeutic options.

Professor Rich Payne from the School of Chemistry is an NHMRC Investigator Leadership Fellow and Deputy Director of the ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) and is a coauthor of the research.

The source of this news is from University of Sydney

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