Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies

Autor: Dan Simionescu, Nishanth Tharayil, Elizabeth Leonard, Wenda Carlyle, Alex Schwarz, Kelvin Ning, Christopher Carsten, Juan Carlos Carrillo Garcia, Alexander Carter, Collin Owens, Agneta Simionescu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Bioengineering, Vol 10, Iss 8, p 936 (2023)
Druh dokumentu: article
ISSN: 2306-5354
DOI: 10.3390/bioengineering10080936
Popis: Pentagalloyl glucose (PGG) is currently being investigated as a non-surgical treatment for abdominal aortic aneurysms (AAAs); however, the molecular mechanisms of action of PGG on the AAA matrix components and the intra-luminal thrombus (ILT) still need to be better understood. To assess these interactions, we utilized peptide fingerprinting and molecular docking simulations to predict the binding of PGG to vascular proteins in normal and aneurysmal aorta, including matrix metalloproteinases (MMPs), cytokines, and fibrin. We performed PGG diffusion studies in pure fibrin gels and human ILT samples. PGG was predicted to bind with high affinity to most vascular proteins, the active sites of MMPs, and several cytokines known to be present in AAAs. Finally, despite potential binding to fibrin, PGG was shown to diffuse readily through thrombus at physiologic pressures. In conclusion, PGG can bind to all the normal and aneurysmal aorta protein components with high affinity, potentially protecting the tissue from degradation and exerting anti-inflammatory activities. Diffusion studies showed that thrombus presence in AAAs is not a barrier to endovascular treatment. Together, these results provide a deeper understanding of the clinical potential of PGG as a non-surgical treatment of AAAs.
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje