This is due, in part, to a lack of fundamental understanding about RNA-ligand interactions including the types of small molecules that bind to RNA structural elements and the RNA structural elements that bind to small molecules. In an effort to better understand RNA-ligand interactions, Abiraterone Sigma we diversified the 2-aminobenzimidazole: Core (2AB) and probed the resulting library for binding to a library of RNA internal loops. We chose the 2AB core for these studies because it is a privileged scaffold for binding RNA based on previous reports. These studies identified that N-methyl pyrrolidine, imidazole, and propylamine diversity elements at the R1 position increase binding to internal loops; variability at the R2 position is well tolerated.

The preferred RNA loop space was also determined for five ligands using a statistical approach and identified trends that lead to selective recognition.
We have developed the first irreversible inhibitors of wild type c-Src kinase. We demonstrate that our irreversible,inhibitors display improved selectivity,potency and selectivity relative to that of their reversible counterparts. Our strategy involves modifying a promiscuous kinase inhibitor with an electrophile to generate covalent inhibitors of c-Src. We applied this methodology to two inhibitor scaffolds that exhibit increased cellular efficacy when rendered irreversible. In addition, we have demonstrated the utility of irreversible inhibitors in studying the conformation of an important loop in kinases that can control inhibitor selectivity and cause drug resistance.

Together, we have developed a general and robust framework for generating selective irreversible inhibitors from reversible, promiscuous inhibitor scaffolds.
ZFtsZ is a guanosine triphosphatase (GTPase) that mediates cytokinesis in bacteria. FtsZ is homologous in structure to eukaryotic tubulin and polymerizes in a similar head-to-tail fashion. The study of tubulin’s function in eukaryotic cells has benefited greatly from specific and potent small molecule inhibitors, including colchicine and taxol. Although many small molecule inhibitors of FtsZ have been reported, none has emerged as a generally useful probe for Modulating bacterial cell division. With Brefeldin_A the goal of establishing a useful and reliable small molecule inhibitor of FtsZ, a broad biochemical cross comparison of reported FtsZ, inhibitors was undertaken.

Several of these molecules, including phenolic natural products, selleck catalog are unselective inhibitors that seem to;derive their activity from the formation of microscopic colloids or aggregates. Other compounds, including the natural product viriditoxin and the drug development candidate PC190723, exhibit no inhibition of GTPase activity Using protocols in this work or under published conditions.