An RNA Aptamer Inhibits a Mutation-Induced Inactivating Misfolding of a Serpin
| العنوان: | An RNA Aptamer Inhibits a Mutation-Induced Inactivating Misfolding of a Serpin |
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| المؤلفون: | Jesper S. Johansen, Lisbeth M. Andersen, Jan K. Jensen, Daniel M. Dupont, Peter A. Andreasen, Thomas J. D. Jørgensen, Morten Beck Trelle, Jeppe B. Madsen |
| المصدر: | Madsen, J B, Andersen, L M, Dupont, D M, Trelle, M B, Johansen, J S, Jensen, J K, Jørgensen, T J D & Andreasen, P A 2016, ' An RNA Aptamer Inhibits a Mutation-Induced Inactivating Misfolding of a Serpin ', Cell Chemical Biology, vol. 23, no. 6, pp. 700–708 . https://doi.org/10.1016/j.chembiol.2016.04.013 Madsen, J B, Andersen, L M, Dupont, D M, Trelle, M B, Johansen, J S, Jensen, J K, Jørgensen, T J D & Andreasen, P A 2016, ' An RNA Aptamer Inhibits a Mutation-Induced Inactivating Misfolding of a Serpin ', Cell Chemical Biology, vol. 23, no. 6, pp. 700-708 . https://doi.org/10.1016/j.chembiol.2016.04.013 |
| بيانات النشر: | Elsevier BV, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, Protein Folding, Proteases, animal structures, Aptamer, medicine.medical_treatment, Clinical Biochemistry, Biology, Serpin, medicine.disease_cause, Biochemistry, Mass Spectrometry, Serine, 03 medical and health sciences, Drug Discovery, Journal Article, medicine, Humans, Molecular Biology, Serpins, Pharmacology, Mutation, Protease, 030102 biochemistry & molecular biology, Deuterium Exchange Measurement, RNA, Aptamers, Nucleotide, Surface Plasmon Resonance, 030104 developmental biology, embryonic structures, Molecular Medicine, Protein folding |
| الوصف: | Most serpins are fast and specific inhibitors of extracellular serine proteases controlling biological processes such as blood coagulation, fibrinolysis, tissue remodeling, and inflammation. The inhibitory activity of serpins is based on a conserved metastable structure and their conversion to a more stable state during reaction with the target protease. However, the metastable state also makes serpins vulnerable to mutations, resulting in disease caused by inactive and misfolded monomeric or polymeric forms ("serpinopathy"). Misfolding can occur either intracellularly (type-I serpinopathies) or extracellularly (type-II serpinopathies). We have isolated a 2'-fluoropyrimidine-modified RNA aptamer, which inhibits a mutation-induced inactivating misfolding of the serpin α1-antichymotrypsin. It is the first agent able to stabilize a type-II mutation of a serpin without interfering with the inhibitory mechanism, thereby presenting a solution for the long-standing challenge of preventing pathogenic misfolding without compromising the inhibitory function. |
| تدمد: | 2451-9456 |
| DOI: | 10.1016/j.chembiol.2016.04.013 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc5b1e44e7bae7e6d201257583c136fd https://doi.org/10.1016/j.chembiol.2016.04.013 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cc5b1e44e7bae7e6d201257583c136fd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 24519456 |
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| DOI: | 10.1016/j.chembiol.2016.04.013 |