FXIIIa-Inhibitor Tridegin
This project is financially supported by the “Deutsche Stiftung für Herzforschung” (German Heart Foundation).
Tridegin is a 66mer peptide that was originally isolated from the salivary gland of the giant Amazon leech Haementeria ghilianii in 1997 [1,2]. So far, it is the only potent and specific peptidic inhibitor of the coagulation factor XIIIa (FXIIIa) which catalyzes the last step of the blood coagulation cascade Thus, FXIIIa is an interesting target for antithrombotic and thrombolytic therapy [3].
In order to characterize the inhibitory mechanism and structure of this interesting peptide in more detail, it was required to gain access to the peptide via different preparation methods (synthetic and recombinant approaches), which we established recently [4,5]. Functional analysis by testing enzyme activity and performing binding assays revealed that the major inhibitory action is localized in the C-terminal part of the peptide, whereas the N-terminal part contributes decisively to binding affinity [4,5]. Furthermore, the disulfide connectivity of both the synthetic and the recombinant peptide was elucidated by mass spectrometric analysis. Subsequently, molecular modeling of the three identified isomers and their molecular docking to the FXIII-A° (PDB ID: 4KTY) structure provided further insight on structure-activity relationships of tridegin [5].
The aim of our present studies is to synthesize and analyze different tridegin variants so as to further increase the understanding of this natural FXIIIa inhibitor and thereby provide the scientific community with a valuable research tool as well as a potential lead structure for the development of FXIIIa inhibitors.
For further information see: https://zedira.com/Blog/Tridegin-as-FXIIIa-inhibitor_118
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