Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies
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 inter...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/10/8/936 |
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| author | Dan Simionescu Nishanth Tharayil Elizabeth Leonard Wenda Carlyle Alex Schwarz Kelvin Ning Christopher Carsten Juan Carlos Carrillo Garcia Alexander Carter Collin Owens Agneta Simionescu |
| author_facet | Dan Simionescu Nishanth Tharayil Elizabeth Leonard Wenda Carlyle Alex Schwarz Kelvin Ning Christopher Carsten Juan Carlos Carrillo Garcia Alexander Carter Collin Owens Agneta Simionescu |
| author_sort | Dan Simionescu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:06:33Z |
| format | Article |
| id | doaj.art-749b85ecce224ee3a316826c704b39d8 |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-11T00:06:33Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-749b85ecce224ee3a316826c704b39d82023-11-19T00:18:05ZengMDPI AGBioengineering2306-53542023-08-0110893610.3390/bioengineering10080936Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking StudiesDan Simionescu0Nishanth Tharayil1Elizabeth Leonard2Wenda Carlyle3Alex Schwarz4Kelvin Ning5Christopher Carsten6Juan Carlos Carrillo Garcia7Alexander Carter8Collin Owens9Agneta Simionescu10Biocompatibility and Tissue Regeneration Laboratory, Department of Bioengineering, Clemson University, Clemson, SC 29634, USAMulti-User Analytical Lab (MUAL) & Metabolomic Core, Clemson University, Clemson, SC 29634, USAMulti-User Analytical Lab (MUAL) & Metabolomic Core, Clemson University, Clemson, SC 29634, USANectero Medical Inc., Mesa, AZ 85281, USANectero Medical Inc., Mesa, AZ 85281, USANectero Medical Inc., Mesa, AZ 85281, USAPRISMA Health, Greenville, SC 29640, USABiocompatibility and Tissue Regeneration Laboratory, Department of Bioengineering, Clemson University, Clemson, SC 29634, USABiocompatibility and Tissue Regeneration Laboratory, Department of Bioengineering, Clemson University, Clemson, SC 29634, USATissue Engineering Laboratory, Department of Bioengineering, Clemson University, Clemson, SC 29634, USATissue Engineering Laboratory, Department of Bioengineering, Clemson University, Clemson, SC 29634, USAPentagalloyl 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.https://www.mdpi.com/2306-5354/10/8/936aneurysmspolyphenolsdiffusionstabilizationdocking simulationselastin |
| spellingShingle | Dan Simionescu Nishanth Tharayil Elizabeth Leonard Wenda Carlyle Alex Schwarz Kelvin Ning Christopher Carsten Juan Carlos Carrillo Garcia Alexander Carter Collin Owens Agneta Simionescu Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies Bioengineering aneurysms polyphenols diffusion stabilization docking simulations elastin |
| title | Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies |
| title_full | Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies |
| title_fullStr | Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies |
| title_full_unstemmed | Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies |
| title_short | Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies |
| title_sort | binding of pentagalloyl glucose to aortic wall proteins insights from peptide mapping and simulated docking studies |
| topic | aneurysms polyphenols diffusion stabilization docking simulations elastin |
| url | https://www.mdpi.com/2306-5354/10/8/936 |
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