Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372277 | Bioorganic & Medicinal Chemistry Letters | 2013 | 8 Pages |
Cyclophilins (Cyps) are ubiquitous proteins that effect the cis–trans isomerization of Pro amide bonds, and are thus crucial to protein folding. CypA is the most prevalent of the ∼19 human Cyps, and plays a crucial role in viral infectivity, most notably for HIV-1 and HCV. Cyclophilins have been shown to play key roles in effective replication of a number of viruses from different families. A drug template for CypA inhibition is cyclosporine A (CsA), a cyclic undecapeptide that simultaneously binds to both CypA and the Ca2+-dependent phosphatase calcineurin (CN), and can attenuate immune responses. Synthetic modifications of the CsA scaffold allows for selective binding to CypA and CN separately, thus providing access to novel, non-immunosuppressive antiviral agents.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide