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Sulfenic Acid (sulfenic + acid)
Selected AbstractsAcid decomposition of omeprazole in the absence of thiol: A differential pulse polarographic study at the static mercury drop electrode (SMDE)JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2006Ali M. Qaisi Abstract The reactions of omeprazole, a potent proton pump inhibitor (PPI), were investigated in the absence of a nucleophile. Reactions were monitored, using differential pulse polarography (DPP) at the static mercury drop electrode (SMDE), in solutions buffered to pH values ranging from 2.0 to 8.0. The fast, sensitive, and selective electrochemical technique facilitated to repeat recordings of successive voltammograms [peak current (nA) vs. peak potential (volts vs. Ag/AgCl saturated with 3.0 M KCl)]. The DPP signals of omeprazole and its degradation products, believed to be due to sulfur functional group (the principal site of electrode reaction), gave advantages over the previously employed UV detection technique. The latter primarily relied on pyridine and benzimidazole analytical signals, which are common reaction products of PPI in aqueous acidic solutions. After peak identification, the resulting current (nA)-time (s) profiles, demonstrated that omeprazole undergoes degradation to form two main stable compounds, the first is the cyclic sulfenamide (D+), previously believed to be the active inhibitor of the H+, K+ -ATPase, the second is omeprazole dimer. This degradation is highly dependant on pH. Unlike previous studies which reported that the lifetime of D+ is few seconds, the cyclic sulfenamide (D+) was found to be stable for up to 5,20 min. The results further indicated that omeprazole converts into the cyclic sulfenamide in an irreversible reaction, consequently, D+ and sulfenic acid (an intermediate which rapidly converts into D+) were not interconvertable. The present work suggested that the sulfenic acid is the active inhibitor in vivo. In addition, the omeprazole reactions, in the absence of the thiol, were not as complicated as were previously reported. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:384,391, 2006 [source] Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acidPROTEIN SCIENCE, Issue 2 2008Freddie R. Salsbury Jr Abstract Cysteine sulfenic acid (Cys-SOH), a reversible modification, is a catalytic intermediate at enzyme active sites, a sensor for oxidative stress, a regulator of some transcription factors, and a redox-signaling intermediate. This post-translational modification is not random: specific features near the cysteine control its reactivity. To identify features responsible for the propensity of cysteines to be modified to sulfenic acid, a list of 47 proteins (containing 49 known Cys-SOH sites) was compiled. Modifiable cysteines are found in proteins from most structural classes and many functional classes, but have no propensity for any one type of protein secondary structure. To identify features affecting cysteine reactivity, these sites were analyzed using both functional site profiling and electrostatic analysis. Overall, the solvent exposure of modifiable cysteines is not different from the average cysteine. The combined sequence, structure, and electrostatic approaches reveal mechanistic determinants not obvious from overall sequence comparison, including: (1) pKas of some modifiable cysteines are affected by backbone features only; (2) charged residues are underrepresented in the structure near modifiable sites; (3) threonine and other polar residues can exert a large influence on the cysteine pKa; and (4) hydrogen bonding patterns are suggested to be important. This compilation of Cys-SOH modification sites and their features provides a quantitative assessment of previous observations and a basis for further analysis and prediction of these sites. Agreement with known experimental data indicates the utility of this combined approach for identifying mechanistic determinants at protein functional sites. [source] | ||||||||||