Transglutaminase-catalyzed covalent anti-myostatin peptide depots
Nature realizes protein and peptide depots by catalyzing covalent bonds with the extracellular matrix (ECM) of tissues. We are translating this natural blueprint for the sustained delivery of a myostatin-inhibiting peptide (Anti-Myo), resulting in an enzyme depot established from injectable solutions. For that, we fused Anti-Myo to the D-domain of insulin-like growth factor I, a transglutaminase (TG) substrate. TG catalyzed the covalent binding of the D-domain to ECM proteins, such as laminin and fibronectin, on bioengineered ECM and in mice. ECM decorated with Anti-Myo suppressed myostatin activity and pathway activation and reduced the differentiation of preconditioned bone marrow-derived macrophages into osteoclasts in vitro.
Authors
- Tessa Lühmann (ORCID: https://orcid.org/0000-0001-7552-6435)
- Lorenz Meinel (ORCID: https://orcid.org/0000-0002-7549-7627)
- Denise Beckmann (ORCID: https://orcid.org/0000-0002-6764-7971)
- Rafael Worschech
- Marcus Gutmann (ORCID: https://orcid.org/0000-0001-6000-7923)
- Alexandra C. Braun (ORCID: https://orcid.org/0000-0002-7398-4755)
- Thomas Pap (ORCID: https://orcid.org/0000-0001-6514-0416)
- Prisca Hamm (ORCID: https://orcid.org/0000-0001-7164-0695)
- Adelheid Korb‐Pap (ORCID: https://orcid.org/0000-0002-0106-903X)
Institutions
- University of Würzburg (DE)
- University Hospital Münster (DE)
- Helmholtz Institute for RNA-based Infection Research (DE)
Publication Details
- Journal
- European Journal of Pharmaceutics and Biopharmaceutics
- Published
- 2024-08-26
- DOI
- https://doi.org/10.1016/j.ejpb.2024.114462
- Citations
- 2
- Primary Topic
- Blood properties and coagulation
- Type
- article
- Field-Weighted Citation Impact
- 0.84
Funders
- Bundesministerium für Bildung und Forschung
- Bundesministerium für Gesundheit
- Julius-Maximilians-Universität Würzburg