Pentosinane, a Post-Translational Modification of Human Proteins with Underappreciated Stability
| العنوان: | Pentosinane, a Post-Translational Modification of Human Proteins with Underappreciated Stability |
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| المؤلفون: | Edward A. deRamon, Venkata R. Sabbasani, Matthew D. Streeter, Yannan Liu, Timothy R. Newhouse, David M. McDonald, David A. Spiegel |
| المصدر: | Journal of the American Chemical Society. 144:21843-21847 |
| بيانات النشر: | American Chemical Society (ACS), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Colloid and Surface Chemistry, Humans, General Chemistry, Protein Processing, Post-Translational, Biochemistry, Catalysis |
| الوصف: | Pentosinane is a structurally complex nonenzymatic post-translational modification of proteins believed to be present in all living things. It falls into the category of advanced glycation end products (AGEs) and is structurally related to the other AGEs pentosidine and glucosepane. Although pentosidine and glucosepane have been widely studied for their role in wide-ranging conditions (e.g., diabetes mellitus, Alzheimer's disease, and human aging), relatively little is known about pentosinane. Interestingly, previous reports have suggested that pentosidine may derive from pentosinane. The (patho)physiological significance of pentosinane in humans is largely unexplored. As a first step to address this knowledge gap, we report herein the first total synthesis of pentosinane. Our synthesis is high yielding (1.7% over seven steps), concise, and enantioselective, and it leverages a strategy for synthesizing 2,5-diaminoimidazoles previously developed by our lab. Access to synthetic pentosinane has allowed us to perform additional studies showing that its oxidation to pentosidine is both pH and oxygen dependent and is substantially slower under physiological conditions than previously believed. Additionally, pentosinane rapidly decomposes under harshly acidic conditions typically employed for pentosidine isolation. Taken together, these results suggest that pentosinane is likely to be more abundant |
| تدمد: | 1520-5126 0002-7863 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::698ee075774f44323d7a3b9712808c31Test https://doi.org/10.1021/jacs.2c09626Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....698ee075774f44323d7a3b9712808c31 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15205126 00027863 |
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