Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by Preventing Ribosome Binding
Abstract
:1. Introduction
2. Results
2.1. The Longer Peptides Have Higher Affinity for RTA than the Shorter Peptides
2.2. Peptides Bind to the Ribosome Binding Site of RTA
2.3. Peptides Compete with Ribosomes for Binding to RTA
2.4. Peptides Inhibit the Depurination Activity of RTA
3. Discussion
4. Materials and Methods
4.1. Peptide Synthesis
4.2. RTA Purification
4.3. Peptide–RTA Interaction
4.4. Peptide Competition Assays
4.5. Inhibition of RTA Depurination
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Peptides | Sequence | MW | KD (µM) * |
---|---|---|---|
P11 | S105DDDMGFGLFD115 | 1218.25 | 196 ± 17 |
P10 | D106DDMGFGLFD115 | 1131.18 | 272 ± 6 |
P9 | D107DMGFGLFD115 | 1016.09 | 309 ± 7 |
P8 | D108MGFGLFD115 | 901.00 | 299 ± 5 |
P7 | M109GFGLFD115 | 785.91 | 294 ± 47 |
P6 | G110FGLFD115 | 654.71 | 399 ± 20 |
P5 | F111GLFD115 | 597.66 | 497 ± 30 |
P4 | G112LFD115 | 450.49 | 451 ± 17 |
P3 | L113FD115 | 393.44 | >10 mM |
Peptide | Sequence | Yeast Ribosome IC50 (µM) * | Rat Ribosome IC50 (µM) * |
---|---|---|---|
P11 | S105DDDMGFGLFD115 | 4.7 ± 0.9 | 31 ± 6.3 |
P10 | D106DDMGFGLFD115 | 7.9 ± 1.7 | 83 ± 18 |
P9 | D107DMGFGLFD115 | 15 ± 1.5 | 142 ± 61 |
P8 | D108MGFGLFD115 | 23 ± 4.4 | 267 ± 80 |
P7 | M109GFGLFD115 | 34 ± 9.5 | NA |
P6 | G110FGLFD115 | 63 ± 13 | NA |
P5 | F111GLFD115 | 121 ± 44 | NA |
P4 | G112LFD115 | 102 ± 45 | NA |
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Li, X.-P.; Kahn, J.N.; Tumer, N.E. Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by Preventing Ribosome Binding. Toxins 2018, 10, 371. https://doi.org/10.3390/toxins10090371
Li X-P, Kahn JN, Tumer NE. Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by Preventing Ribosome Binding. Toxins. 2018; 10(9):371. https://doi.org/10.3390/toxins10090371
Chicago/Turabian StyleLi, Xiao-Ping, Jennifer N. Kahn, and Nilgun E. Tumer. 2018. "Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by Preventing Ribosome Binding" Toxins 10, no. 9: 371. https://doi.org/10.3390/toxins10090371