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Re-emerging Aspartic Protease Targets: Examining Major Aspartyl Peptidase 1 as a Target for Antifungal Drug Discovery

J Med Chem. 2021-05; 
Robin Kryštůfek, Pavel Šácha, Jana Starková, Jiří Brynda, Martin Hradilek, Eva Tloušt'ová, Justyna Grzymska, Wioletta Rut, Michael J Boucher, Marcin Drąg, Pavel Majer, Miroslav Hájek, Pavlína Řezáčová, Hiten D Madhani, Charles S Craik, Jan Konvalinka
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GenParts™ DNA Fragments … Full-length cnap1 gene cDNA encoding May1 (CNAG_05872) generated in silico in pUC57 plasmid was purchased from Genscript. The 17-434 fragment was PCR amplified using primers 5′-AAAAAGATCTGCACCAAGCAACAGCGTC-3′ and 5′-… Get A Quote

摘要

Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate spe... More

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