Application of Lipophilic Prodrug Charge Masking Strategy to Obtain Novel, Potential Oxytocin Prodrugs
Abstract
1. Introduction
2. Results
2.1. Peptide Synthesis
2.2. PAMPA
2.3. Permeability Experiments in the Caco-2 Model
3. Discussion
4. Materials and Methods
4.1. Peptide Synthesis
4.2. PAMPA
4.3. Caco-2 Cell Model Assays
4.3.1. Caco-2 Intestine Epithelial Model
4.3.2. Cytotoxicity Test
4.3.3. Transepithelial Transport Experiment
4.4. LC-MS Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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No | Name a | Structure | Calculated [M+H]+ | Found [M+H]+ | CLogP b |
---|---|---|---|---|---|
1. | OT | Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1004.444 | 1007.514 | −0.654 |
2. | Et-OT | Et-Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1079.466 | 1079.586 | 0.461 |
3. | MeOEt-OT | MeOEt-Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1109.476 | 1109.520 | 0.129 |
4. | Prop-OT | Prop-Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1093.481 | 1093.491 | 0.990 |
5. | But-OT | But-Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1107.497 | 1107.541 | 1.519 |
6. | Hoc-OT | Hoc-Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1135.528 | 1135.622 | 2.577 |
7. | Oct-OT | Oct-Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1163.559 | 1163.635 | 3.635 |
8. | Dec-OT | Dec-Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1191.591 | 1191.611 | 4.693 |
9. | Dod-OT | Dod-Cys(&)-Tyr-Ile-Gln-Asn-Cys(&)-Pro-Leu-Gly-NH2 | 1219.622 | 1219.691 | 5.751 |
Compound | Papp (10−6 cm/s) ± SD | Mass Retention |
---|---|---|
Caffeine | 21.99 ± 11.16 | 26% |
Atenolol | 1.24 ± 1.28 | 12% |
OT | 2.22 ± 0.21 | 19% |
Et-OT | 2.78 ± 0.17 | 16% |
MeOEt-OT | 2.37 ± 0.52 | 15% |
Prop-OT | 2.97 ± 0.64 | 33% |
But-OT | 2.20 ± 0.30 | 30% |
Hoc-OT | 4.67 ± 0.66 | 43% |
Oct-OT | 5.93 ± 0.86 | 33% |
Dec-OT | 9.28 ± 6.11 | 32% |
Dod-OT | 1.08 ± 0.95 | 67% |
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Gitlin-Domagalska, A.; Olejnik, A.; Ruczyński, J.; Starego, D.; Ptaszyńska, N.; Łęgowska, A.; Dębowski, D.; Gilon, C.; Rolka, K. Application of Lipophilic Prodrug Charge Masking Strategy to Obtain Novel, Potential Oxytocin Prodrugs. Int. J. Mol. Sci. 2025, 26, 4772. https://doi.org/10.3390/ijms26104772
Gitlin-Domagalska A, Olejnik A, Ruczyński J, Starego D, Ptaszyńska N, Łęgowska A, Dębowski D, Gilon C, Rolka K. Application of Lipophilic Prodrug Charge Masking Strategy to Obtain Novel, Potential Oxytocin Prodrugs. International Journal of Molecular Sciences. 2025; 26(10):4772. https://doi.org/10.3390/ijms26104772
Chicago/Turabian StyleGitlin-Domagalska, Agata, Anna Olejnik, Jarosław Ruczyński, Dominika Starego, Natalia Ptaszyńska, Anna Łęgowska, Dawid Dębowski, Chaim Gilon, and Krzysztof Rolka. 2025. "Application of Lipophilic Prodrug Charge Masking Strategy to Obtain Novel, Potential Oxytocin Prodrugs" International Journal of Molecular Sciences 26, no. 10: 4772. https://doi.org/10.3390/ijms26104772
APA StyleGitlin-Domagalska, A., Olejnik, A., Ruczyński, J., Starego, D., Ptaszyńska, N., Łęgowska, A., Dębowski, D., Gilon, C., & Rolka, K. (2025). Application of Lipophilic Prodrug Charge Masking Strategy to Obtain Novel, Potential Oxytocin Prodrugs. International Journal of Molecular Sciences, 26(10), 4772. https://doi.org/10.3390/ijms26104772