التفاصيل البيبلوغرافية
| العنوان: |
Rapid Optimization of the Metabolic Stability of a Human Immunodeficiency Virus Type‑1 Capsid Inhibitor Using a Multistep Computational Workflow |
| المؤلفون: |
Megan E. Meuser (10344177), Poli Adi Narayana Reddy (10344180), Alexej Dick (8780288), Jean Marc Maurancy (10344183), Joseph M. Salvino (1265199), Simon Cocklin (2093152) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Neuroscience, Physiology, Pharmacology, Cancer, Hematology, Infectious Diseases, Virology, Space Science, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Information Systems not elsewhere classified, inhibitor PF -74, Multistep Computational Workflow Poor, stability, design CA compounds, HIV, PF -74, workflow, novel multistep computationally, immunodeficiency virus type, CA interprotomer pocket, PF -74 analogs |
| الوصف: |
Poor metabolic stability of the human immunodeficiency virus type-1 (HIV-1) capsid (CA) inhibitor PF-74 is a major concern in its development toward clinical use. To improve on the metabolic stability, we employed a novel multistep computationally driven workflow, which facilitated the rapid design of improved PF-74 analogs in an efficient manner. Using this workflow, we designed three compounds that interact specifically with the CA interprotomer pocket, inhibit HIV-1 infection, and demonstrate enantiomeric preference. Moreover, using this workflow, we were able to increase the metabolic stability 204-fold in comparison to PF-74 in only three analog steps. These results demonstrate our ability to rapidly design CA compounds using a novel computational workflow that has improved metabolic stability over the parental compound. This workflow can be further applied to the redesign of PF-74 and other promising inhibitors with a stability shortfall. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Rapid_Optimization_of_the_Metabolic_Stability_of_a_Human_Immunodeficiency_Virus_Type_1_Capsid_Inhibitor_Using_a_Multistep_Computational_Workflow/14262006 |
| DOI: |
10.1021/acs.jmedchem.0c01810.s005 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.0c01810.s005 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.D9BD9F40 |
| قاعدة البيانات: |
BASE |