Article ; Online: Structural Basis of Antisickling Effects of Selected FDA Approved Drugs: A Drug Repurposing Study.
Current computer-aided drug design
2018 Volume 14, Issue 2, Page(s) 106–116
Abstract: Introduction: Sickle cell disease is characterized by a point mutation involving substitution of glutamic acid at position 6 to valine. Encoded in this hydrophobic mutation is both an intrinsic capacity for the beta globin molecules to assemble into ... ...
| Abstract | Introduction: Sickle cell disease is characterized by a point mutation involving substitution of glutamic acid at position 6 to valine. Encoded in this hydrophobic mutation is both an intrinsic capacity for the beta globin molecules to assemble into thermodynamically favoured polymeric states as well as a rational way of interrupting the aggregation. Methods: In this work, starting with a theoretical model that employs occlusive binding onto the beta globin aggregation surface and using a range of computational methods and an effective energy for screening, a number of FDA approved drugs with computed aggregation inhibitory activities were identified. Results and conclusion: The validity of the model was confirmed using sickling tests, after which pharmacophore models as well the structural basis for the observed antisickling effects were identified. |
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| MeSH term(s) | Anemia, Sickle Cell/drug therapy ; Anemia, Sickle Cell/genetics ; Anemia, Sickle Cell/metabolism ; Antisickling Agents/chemistry ; Antisickling Agents/pharmacology ; Drug Approval ; Drug Repositioning/methods ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Point Mutation ; Protein Aggregates/drug effects ; United States ; United States Food and Drug Administration ; beta-Globins/genetics ; beta-Globins/metabolism |
| Chemical Substances | Antisickling Agents ; Protein Aggregates ; beta-Globins |
| Language | English |
| Publishing date | 2018-01-29 |
| Publishing country | United Arab Emirates |
| Document type | Journal Article |
| ISSN | 1875-6697 |
| ISSN (online) | 1875-6697 |
| DOI | 10.2174/1573409914666180129163711 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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