دورية أكاديمية
Ligand Accessibility and Bioactivity of a Hormone-Dendrimer Conjugate Depend on pH and pH History
| العنوان: | Ligand Accessibility and Bioactivity of a Hormone-Dendrimer Conjugate Depend on pH and pH History |
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| المؤلفون: | Kim, Sung Hoon, Madak-Erdogan, Zeynep, Bae, Sung Chul, Carlson, Kathryn E., Mayne, Christopher G., Granick, Steve, Katzenellenbogen, Benita S., Katzenellenbogen, John, A. |
| بيانات النشر: | AMER CHEMICAL SOC |
| سنة النشر: | 2015 |
| المجموعة: | ScholarWorks@UNIST (Ulsan National Institute of Science and Technology) |
| الوصف: | Estrogen conjugates with a polyamidoamine (PAMAM) dendrimer have shown remarkably selective regulation of the nongenomic actions of estrogens in target cells. In response to pH changes, however, these estrogen-dendrimer conjugates (EDCs) display a major morphological transition that alters the accessibility of the estrogen ligands that compromises the bioactivity of the EDC. A sharp break in dynamic behavior near pH 7 occurs for three different ligands on the surface of a PAMAM-G6 dendrimer: a fluorophore (tetramethylrhodamine [TMR]) and two estrogens (17 alpha-ethynylestradiol and diphenolic acid). Collisional quenching and time-resolved fluorescence anisotropy experiments with TMR-PAMAM revealed high ligand shielding above pH 7 and low shielding below pH 7. Furthermore, when the pH was cycled from 8.5 (conditions of ligand-PAMAM conjugation) to 4.5 (e.g., endosome/lysosome) and through 6.5 (e.g., hypoxic environment) back to pH 8.5, the 17 alpha-ethynylestradiol- and diphenolic acid-PAMAM conjugates experienced a draniatic, irreversible loss in cell stimulatory activity; dynamic NMR studies indicated that the hormonal ligands had become occluded within the more hydrophobic core of the PAMAM dendrimer. Thus, the active state of these estrogen-dendrimer conjugates appears to be metastable. This pH-dependent irreversible masking of activity is of considerable relevance to the design of drug conjugates with amine-bearing PAMAM dendrimers. ; close |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| ردمك: | 978-0-00-359962-6 0-00-359962-0 |
| تدمد: | 0002-7863 |
| العلاقة: | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.137, no.32, pp.10326 - 10335; https://scholarworks.unist.ac.kr/handle/201301/20740Test; 1821; 2381; 27241; 2-s2.0-84939865433; 000359962000054 |
| DOI: | 10.1021/jacs.5b05952 |
| الإتاحة: | https://doi.org/10.1021/jacs.5b05952Test https://scholarworks.unist.ac.kr/handle/201301/20740Test |
| رقم الانضمام: | edsbas.664E7FE4 |
| قاعدة البيانات: | BASE |
| ردمك: | 9780003599626 0003599620 |
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| تدمد: | 00027863 |
| DOI: | 10.1021/jacs.5b05952 |