Pan-Amyloid Reactive Peptides p5+14 and p5R Exhibit Specific Charge-Dependent Binding to Glycosaminoglycans
Abstract
1. Introduction
2. Results
2.1. Structural Models of Peptides p5+14 and p5R
2.2. Polybasic Peptides p5+14 and p5R Bind to Systemic Amyloid Deposits
2.3. Glycosaminoglycan Binding of Biotinylated Peptides p5+14 and p5R
2.4. Heparan Sulfate Binding of Biotinylated Peptides p5+14 and p5R
3. Discussion
4. Materials and Methods
4.1. Peptide Synthesis
4.2. Peptide Structure Modeling
4.3. Circular Dichroism
4.4. Glycosaminoglycan and Heparan Sulfate Arrays
4.5. Radiolabeling of Peptide p5+14 and PET/CT Imaging
4.6. Data Visualization and Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Peptide | Sequence | Molecular Weight 1 | Amino Acid Length | Basic Residues | Average Charge per Residue |
---|---|---|---|---|---|
p5+14 | GGGYS KAQKA QAKQA KQAQK AQKAQ AKQAK QAQKA QKAQA KQAKQ | 4766.5 | 45 | 12 | 0.267 |
p5R | GGGYS RAQRA QARQA RQAQR AQRAQ ARQAR Q | 3481.8 | 31 | 8 | 0.258 |
Biotinyl-Peptide | Sulfations (All GAGs) | Sulfations (heparin and HS Only) | Sulfations (Non-Heparin and HS) | |
---|---|---|---|---|
p5+14 | Pearson r | 0.7925 | 0.9181 | 0.5309 |
p-value | <0.0001 | <0.0001 | 0.0063 | |
p5R | Pearson r | 0.7215 | 0.9223 | 0.3714 |
p-value | <0.0001 | <0.0001 | 0.0676 |
Apparent EC50: µg/mL (Molarity) | ||||
---|---|---|---|---|
Biotinyl-Peptide | Heparin (GAG16) | Chondroitin Sulfate AC (GAG22) | Chondroitin Sulfate D (GAG28) | Heparan Sulfate (GAG46) |
p5+14 | 1.198 (251.3 nM) | 3.376 (708.2 nM) | 1.334 (279.9 nM) | 0.932 (195.5 nM) |
p5R | 4.537 (1.303 µM) | nd * | 5.758 (1.65 µM) | 6.792 (1.95 µM) |
Biotinyl-Peptide | HS Total Sulfations (Net Charge) | HS Sulfations/Saccharide (Charge Density) | |
---|---|---|---|
p5+14 | Pearson r | 0.9764 | 0.9250 |
p-values | <0.0001 | <0.0001 | |
p5R | Pearson r | 0.924 | 0.9446 |
p-values | <0.0001 | <0.0001 |
Apparent Ec50: µg/mL (Molarity) | ||||
---|---|---|---|---|
Biotinyl-Peptide | HS13 | HS16 | HS22 | HS24 |
p5+14 | - | 0.6685 (140.2 nM) | 0.4734 (99.31 nM) | 0.4482 (94.03 nM) |
p5R | 2.338 (671.5 nM) | 1.930 (554.3 nM) | 1.241 (356.4 nM) | 1.358 (390.0 nM) |
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Hancock, T.J.; Williams, A.D.; Foster, J.S.; Wall, J.S.; Martin, E.B. Pan-Amyloid Reactive Peptides p5+14 and p5R Exhibit Specific Charge-Dependent Binding to Glycosaminoglycans. Pharmaceuticals 2025, 18, 1340. https://doi.org/10.3390/ph18091340
Hancock TJ, Williams AD, Foster JS, Wall JS, Martin EB. Pan-Amyloid Reactive Peptides p5+14 and p5R Exhibit Specific Charge-Dependent Binding to Glycosaminoglycans. Pharmaceuticals. 2025; 18(9):1340. https://doi.org/10.3390/ph18091340
Chicago/Turabian StyleHancock, Trevor J., Angela D. Williams, James S. Foster, Jonathan S. Wall, and Emily B. Martin. 2025. "Pan-Amyloid Reactive Peptides p5+14 and p5R Exhibit Specific Charge-Dependent Binding to Glycosaminoglycans" Pharmaceuticals 18, no. 9: 1340. https://doi.org/10.3390/ph18091340
APA StyleHancock, T. J., Williams, A. D., Foster, J. S., Wall, J. S., & Martin, E. B. (2025). Pan-Amyloid Reactive Peptides p5+14 and p5R Exhibit Specific Charge-Dependent Binding to Glycosaminoglycans. Pharmaceuticals, 18(9), 1340. https://doi.org/10.3390/ph18091340