d-Amino Acid Peptide Residualizing Agents for Protein Radioiodination: Effect of Aspartate for Glutamate Substitution
Abstract
1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. General
3.2. Single Domain Antibody Fragment, Cells, and Culture Conditions
3.3. Synthesis
3.3.1. Mal-d-GDDDK (1)
3.3.2. TB-Mal-d-GDDDK (2)
3.3.3. IB-Mal-d-GDDDK (3)
3.4. Radiochemistry
3.5. Labeling of sdAb
3.6. Evaluation of Protein-Associated Activity and Immunoreactivity
3.7. Determination of Binding Affinity (KD)
3.8. Paired-Label Internalization Assay
3.9. Paired-Label Biodistribution
4. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the d-amino acids standards and their precursors are available from the authors. |
Organ/Tissue | %ID/g 1 | |||||
---|---|---|---|---|---|---|
1 h | 4 h | 24 h | ||||
I-125 | I-131 | I-125 | I-131 | I-125 | I-131 | |
Liver | 4.15 ± 1.12 | 1.99 ± 0.50 | 4.59 ± 0.53 | 1.73 ± 0.09 | 2.52 ± 0.71 | 0.56 ± 0.17 |
Spleen | 2.28 ± 1.00 | 1.05 ± 0.34 | 1.67 ± 0.69 | 0.73 ± 0.17 | 1.68 ± 0.55 | 0.36 ± 0.12 |
Lungs | 10.34 ± 2.37 | 4.81 ± 0.93 | 7.00 ± 2.13 | 1.86 ± 0.29 | 2.30 ± 0.68 | 0.52 ± 0.35 |
Heart | 1.34 ± 0.37 | 0.99 ± 0.34 | 0.67 ± 0.12 | 0.35 ± 0.01 | 0.25 ± <0.01 | 0.05 ± 0.01 |
Kidneys | 127.5 ± 18.7 | 271.4 ± 66.6 | 132.2 ± 31.1 | 201.1 ± 41.1 | 94.6 ± 22.9 2 | 81.4 ± 28.8 |
Stomach | 0.80 ± 0.46 2 | 0.83 ± 0.49 | 0.79 ± 0.30 2 | 0.80 ± 0.31 | 0.14 ± 0.08 2 | 0.06 ± 0.04 |
Small intestine | 1.20 ± 0.59 2 | 1.18 ± 0.60 | 0.83 ± 0.05 2 | 0.77 ± 0.06 | 0.13 ± 0.03 | 0.05 ± 0.01 |
Large intestine | 0.47 ± 0.12 2 | 0.43 ± 0.12 | 1.89 ± 1.14 2 | 1.84 ± 1.13 | 0.33 ± 0.20 | 0.15 ± 0.11 |
Thyroid | 0.06 ± 0.05 2 | 0.07 ± 0.07 | 0.05 ± 0.02 2 | 0.05 ± 0.02 | 0.08 ± 0.02 2 | 0.09 ± 0.02 |
Muscle | 0.82 ± 0.12 | 0.58 ± 0.05 | 0.26 ± 0.09 2 | 0.22 ± 0.05 | 0.13 ± 0.02 | 0.03 ± 0.01 |
Blood | 2.20 ± 0.65 | 2.00 ± 0.68 | 0.49 ± 0.14 2 | 0.45 ± 0.22 | 0.07 ± 0.01 | 0.05 ± 0.01 |
Bone | 0.68 ± 0.13 2 | 0.64 ± 0.11 | 0.27 ± 0.04 2 | 0.28 ± 0.09 | 0.17 ± 0.02 2 | 0.10 ± 0.04 |
Tumor | 4.36 ± 0.77 2 | 4.82 ± 1.00 | 3.28 ± 1.03 2 | 3.49 ± 0.87 | 1.91 ± 0.32 2 | 1.88 ± 0.39 |
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Pruszynski, M.; Kang, C.M.; Koumarianou, E.; Vaidyanathan, G.; Zalutsky, M.R. d-Amino Acid Peptide Residualizing Agents for Protein Radioiodination: Effect of Aspartate for Glutamate Substitution. Molecules 2018, 23, 1223. https://doi.org/10.3390/molecules23051223
Pruszynski M, Kang CM, Koumarianou E, Vaidyanathan G, Zalutsky MR. d-Amino Acid Peptide Residualizing Agents for Protein Radioiodination: Effect of Aspartate for Glutamate Substitution. Molecules. 2018; 23(5):1223. https://doi.org/10.3390/molecules23051223
Chicago/Turabian StylePruszynski, Marek, Choong Mo Kang, Eftychia Koumarianou, Ganesan Vaidyanathan, and Michael R. Zalutsky. 2018. "d-Amino Acid Peptide Residualizing Agents for Protein Radioiodination: Effect of Aspartate for Glutamate Substitution" Molecules 23, no. 5: 1223. https://doi.org/10.3390/molecules23051223
APA StylePruszynski, M., Kang, C. M., Koumarianou, E., Vaidyanathan, G., & Zalutsky, M. R. (2018). d-Amino Acid Peptide Residualizing Agents for Protein Radioiodination: Effect of Aspartate for Glutamate Substitution. Molecules, 23(5), 1223. https://doi.org/10.3390/molecules23051223