7jty: Difference between revisions
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ | [https://www.uniprot.org/uniprot/GANAB_MOUSE GANAB_MOUSE] Cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins. | ||
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== Publication Abstract from PubMed == | |||
Most enveloped viruses rely on the host cell endoplasmic reticulum (ER) quality control (QC) machinery for proper folding of glycoproteins. The key ER alpha-glucosidases (alpha-Glu) I and II of the ERQC machinery are attractive targets for developing broad-spectrum antivirals. Iminosugars based on deoxynojirimycin have been extensively studied as ER alpha-glucosidase inhibitors; however, other glycomimetic compounds are less established. Accordingly, we synthesized a series of N-substituted derivatives of valiolamine, the iminosugar scaffold of type 2 diabetes drug voglibose. To understand the basis for up to 100,000-fold improved inhibitory potency, we determined high-resolution crystal structures of mouse ER alpha-GluII in complex with valiolamine and 10 derivatives. The structures revealed extensive interactions with all four alpha-GluII subsites. We further showed that N-substituted valiolamines were active against dengue virus and SARS-CoV-2 in vitro. This study introduces valiolamine-based inhibitors of the ERQC machinery as candidates for developing potential broad-spectrum therapeutics against the existing and emerging viruses. | |||
N-Substituted Valiolamine Derivatives as Potent Inhibitors of Endoplasmic Reticulum alpha-Glucosidases I and II with Antiviral Activity.,Karade SS, Hill ML, Kiappes JL, Manne R, Aakula B, Zitzmann N, Warfield KL, Treston AM, Mariuzza RA J Med Chem. 2021 Dec 23;64(24):18010-18024. doi: 10.1021/acs.jmedchem.1c01377. , Epub 2021 Dec 6. PMID:34870992<ref>PMID:34870992</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
<references/> | <references/> | ||