Michael acceptor peptidomimetics

Zedira designed peptidomimetic blockers bearing a michael acceptor pharmacophore.
The electrophilic α,β-unsaturated carbonyl compounds are attacked by the active site cysteine residue (1) to form an irreversible complex (2,3).

Michael acceptor peptidomimetics meachanism

The peptidic lead compound Z013 (ZED754) was used to cocrystallize with tissue transglutaminase. The picture shows the binding mode to the active site. The scaffold was subsequently optimized using medicinal chemistry.
Our clinical candidate ZED1227 is the first TG inhibitor in the clinics.
Compound ZED1301 (A108) is a potent FXIII inhibitor.

Structure of inhibited tissue transglutaminase
Structure of inhibited tissue transglutaminase.
The inhibitor (shown in cyan) is covalently bound by a Michael addition reaction to the active site Cys 277 (yellow surface), which is located in the catalytic tunnel. It mimics the peptide substrates. The main part of the inhibitor fits onto the protein surface, forming several hydrogen bonds and stabilizing the open conformation
(Lindemann et al., XX Int. Med.Chem. Symp. 2008).

Art. No.
A108 Ac-(D)-Asp-MA-Nle-Nle-Leu-Pro-Trp-Pro-OH, "ZED1301"
5 mg
500 €
B015 Biotin-Ahx-MA-QPL-OMe
10 mg
500 €
10 mg
500 €


  • Zedira offers a huge portfolio of reliable specialist transglutaminase related products meant to catalyze research and development, both in academia and industry.


  • imageSuccessful ISO9001:2015 recertification
  • Dr. Falk Pharma and Zedira announce start of the phase 2a proof of concept study of ZED1227 for the treatment of non-alcoholic fatty liver disease (NAFLD)
  • Zedira publication - Features of ZED1227: The First-In-Class Tissue Transglutaminase Inhibitor Undergoing Clinical Evaluation for the Treatment of Celiac Disease
  • Dr. Falk Pharma and Zedira announce start of the phase 2b real-life study of ZED1227 for the treatment of Celiac Disease
  • imageDr. Falk Pharma and Zedira announce successful completion of the phase 2a proof-of-concept study of ZED1227 for the treatment of Celiac Disease
  • imageDr. Falk Pharma und Zedira verkünden den erfolgreichen Abschluss der Phase 2a-Studie mit ZED1227 zur Behandlung von Zöliakie
  • imageReversibly acting transglutaminase 2 inhibitors: drug candidates for the treatment of fibrosis


  • DZG Aktuell: „Aufruf zur Teilnahme an einer weiteren Wirksamkeitsstudie mit dem Studienmedikament ZED1227“
  • imageDesign of Oral FXIIIa Blockers as Safer Anticoagulants – Mission Impossible?
  • imageMicrobial transglutaminase (MTG) enables efficient and site-specific conjugation to native antibodies without the need of antibody engineering


  • 19th International Celiac Disease Symposium

    19.10.2022 - 22.10.2022
    Sorrento, Italy