Common Pharmacophore of Structurally Distinct Small-Molecule Inhibitors of Intracellular Retrograde Trafficking of Ribosome Inactivating Proteins
نویسندگان
چکیده
منابع مشابه
Common Pharmacophore of Structurally Distinct Small-Molecule Inhibitors of Intracellular Retrograde Trafficking of Ribosome Inactivating Proteins
We reported previously (±)-2-(5-methylthiophen-2-yl)-3-phenyl-2,3-dihydroquinazolin-4(1H)-one [(±)-Retro-2(cycl)] as the chemical structure of Retro-2 that showed mouse protection against ricin, a notorious ribosome inactivating protein (RIP). Herein we report our chemical resolution of (±)-Retro-2(cycl), analog synthesis, and cell-based evaluation showing that the two optically pure enantiomer...
متن کاملSmall-Molecule Inhibitor Leads of Ribosome-Inactivating Proteins Developed Using the Doorstop Approach
Ribosome-inactivating proteins (RIPs) are toxic because they bind to 28S rRNA and depurinate a specific adenine residue from the α-sarcin/ricin loop (SRL), thereby inhibiting protein synthesis. Shiga-like toxins (Stx1 and Stx2), produced by Escherichia coli, are RIPs that cause outbreaks of foodborne diseases with significant morbidity and mortality. Ricin, produced by the castor bean plant, is...
متن کاملRibosome-inactivating proteins.
The main results of the research performed in the last 30 years on ribosome-inactivating proteins (RIPs) are reviewed, with emphasis on the new, controversial and uncertain aspects. The nature, distribution, mechanism of action and properties of these proteins are briefly reported, together with their possible applications. A pattern appears of a still largely unexplored subject, whose role in ...
متن کاملRibosome-inactivating proteins
Ribosome-inactivating proteins (RIPs) were first isolated over a century ago and have been shown to be catalytic toxins that irreversibly inactivate protein synthesis. Elucidation of atomic structures and molecular mechanism has revealed these proteins to be a diverse group subdivided into two classes. RIPs have been shown to exhibit RNA N-glycosidase activity and depurinate the 28S rRNA of the...
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Protein kinases have emerged as one of the major drug target classes that are amenable to the development of small molecule inhibitors. They share a conserved structural similarity in the region of the ATP binding site, where most inhibitors interact. Using a pharmacophore approach, we have explored the features of protein-ligand interactions for a set of 220 kinase crystal structures from the ...
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ژورنال
عنوان ژورنال: Scientific Reports
سال: 2013
ISSN: 2045-2322
DOI: 10.1038/srep03397