Naturally occurring inhibitors

The FXIIIa-blocker Tridegin is a 66 amino acid polypeptide present in the saliva of the giant Amazon leech Haementeria ghilianii. Tridegin is neither a competitive inhibitor nor an unspecific thiol-group blocking agent. The inhibition mechanism is unknown so far. Finney et al. (Biochem. J. 1997, 324:797-805) reported an IC₅₀ of about 10 nM for factor XIIIa, whereas Sicker (Ph.D. thesis, 2008) measured an IC₅₀ of 2.5 μM for the recombinant protein.

Using recombinant Tridegin, we determined the IC₅₀ -values against FXIIIa of 0.4 μM (T036) and 1.8 μM (F001) depending on the assay used (Product No. indicated in brackets). Human TG2 is not inhibited by recombinant Tridegin at concentrations up to 10 μM.
Further, some microorganism-derived unspecific “factor XIII blockers” with IC₅₀ -values in the micromolar range have been described, e.g., the antifungal antibiotic Cerulenin (Tymiak et al., J. Antibiot. 1993, 46:204-6).