A Nanomolar-Potency Small Molecule Inhibitor of Regulator of G-Protein Signaling Proteins was written by Blazer, Levi L.;Zhang, Haoming;Casey, Emma M.;Husbands, Stephen M.;Neubig, Richard R.. And the article was included in Biochemistry in 2011.Electric Literature of C8H6FNS This article mentions the following:
Regulators of G-protein signaling (RGS) proteins are potent neg. modulators of signal transduction through G-protein-coupled receptors. They function by binding to activated (GTP-bound) Gα subunits and accelerating the rate of GTP hydrolysis. Modulation of RGS activity by small mols. is an attractive mechanism for fine-tuning GPCR signaling for therapeutic and research purposes. Here we describe the pharmacol. properties and mechanism of action of CCG-50014, the most potent small mol. RGS inhibitor to date. It has an IC50 for RGS4 of 30 nM and is >20-fold selective for RGS4 over other RGS proteins. CCG-50014 binds covalently to the RGS, forming an adduct on two cysteine residues located in an allosteric regulatory site. It is not a general cysteine alkylator as it does not inhibit activity of the cysteine protease papain at concentrations >3000-fold higher than those required to inhibit RGS4 function. It is also >1000-fold more potent as an RGS4 inhibitor than are the cysteine alkylators N-ethylmaleimide and iodoacetamide. Anal. of the cysteine reactivity of the compound shows that compound binding to Cys107 in RGS8 inhibits Gα binding in a manner that can be reversed by cleavage of the compound-RGS disulfide bond. If the compound reacts with Cys160 in RGS8, the adduct induces RGS denaturation, and activity cannot be restored by removal of the compound The high potency and good selectivity of CCG-50014 make it a useful tool for studying the functional roles of RGS4. In the experiment, the researchers used many compounds, for example, 4-Fluorobenzylisothiocyanate (cas: 2740-88-7Electric Literature of C8H6FNS).
4-Fluorobenzylisothiocyanate (cas: 2740-88-7) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Electric Literature of C8H6FNS
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics