1. Development of a Raltegravir-based Photoaffinity-Labeled Probe for Human Immunodeficiency Virus-1 Integrase Capture
- Author
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Pala, Nicolino, Esposito, Francesca, Tramontano, Enzo, Singh, Pankaj Kumar, Sanna, Vanna, Carcelli, Mauro, Haigh, Lisa D, Satta, Sandro, and Sechi, Mario
- Subjects
Raltegravir ,Medicinal and Biomolecular Chemistry ,Infectious Diseases ,HIV-1 integrase inhibitors ,Photoaffinity labeling ,Organic Chemistry ,HIV/AIDS ,Pharmacology and Pharmaceutical Sciences ,Molecular recognition ,Infection - Abstract
Photoaffinity labeling (PAL) is one of the upcoming and powerful tools in the field of molecular recognition. It includes the determination of dynamic parameters, such as the identification and localization of the target protein and the site of drug binding. In this study, a photoaffinity-labeled probe for full-length human immunodeficiency virus-1 integrase (HIV-1 IN) capture was designed and synthesized, following the structure of the FDA-approved drug Raltegravir. This photoprobe was found to retain the HIV IN inhibitory potential in comparison with its parent molecule and demonstrates the ability to label the HIV-1 IN protein. Putative photoprobe/inhibitor binding sites near the catalytic site were then identified after protein digestion coupled to mass and molecular modeling analyses.
- Published
- 2020