Thiol-disulfide chemistry

The free-radical chemistry of fluoroalkanesulfenyl chlorides with hydrocarbons was also investigated [S, 9], Depending upon the structures of the sulfenyl chloride and the hydrocarbon, these reactions yield as major products up to three of the following four types of organic compounds thiols, disulfides, sulfides, and chlorohydrocarbons (equation 6), Perfluoroisobutanesulfenyl chloride is unique m that the only major products detected are the thiol and chlorohydrocarbon [ ] (equation 6) (Table 3). 

The following sections detail the chemistry undergone by specific transfer agents that react by atom or group transfer by a homolytic substitution mechanism. Thiols, disulfides, and sulfides arc covered in Sections 6.2.2.1,6.2.2.2 and 6.2.2.3 respectively, halocarbons in Section 6.2.2.4, and solvents and other agents in Section 6.2.2.5. The transfer constant data provided have not been critically... 

These early studies clearly revealed the inherent problems of the chemistry for site-directed formation of unsymmetrical disulfides that has to avoid formation of homodimers. These can result from (i) slow rates of activation of the cysteine peptide, (ii) disproportionation of the activated cysteine species, (in) weak activation and thus slow thiolysis by the second cysteine component and thus its oxidation to the homodimer as well as thiol/ disulfide exchange reactions on the unsymmetrical disulfide present in the reaction media. The latter side reactions are partly controlled by operating in degassed argon-saturated buffers or in organic solvents and preferably under acidic conditions where thiol/disulfide exchange reactions on the nonactivated disulfides, i.e. on the target unsymmetrical cystine peptide occurs at slow rates. 

Cech, T. R. (1990). Self-splicing of group I introns. Annu. Rev. Biochem. 59, 543—568. Cohen, S. B., and Cech, T. R. (2001). Engineering disulfide cross-links in RNA using thiol-disulfide interchange chemistry. Cun. Protoc. Nucleic Acid Chem. Chapter 5, Unit 5 1. 

The range of functionality provided by the 20 amino acids found in proteins consists of weak acids and bases, nucleophiles, hydrogen bond donors and acceptors, and the redox active thiol/disulfide. This limited range of chemistry is inadequate for the catalysis of many reactions found to occur in biological systems. Therefore, a variety of small organic molecules, called cofactors, coenzymes, or vitamins, have evolved to broaden the limited range of chemistry that can be catalyzed by simple proteins. 

Tsarevsky, N.V. Matyjaszewski, K. Combining atom transfer radical polymerization and disulfide/thiol redox chemistry A route to well-defined (bio)degradable polymeric materials. Macromolecules 2005,38 (8), 3087-3092. 

Note that the equilibrium constants describing the formation of library members from their building blocks is not always chemically realistic. For example, in disulfide chemistry the conversion of thiols into disulfides is an irreversible process. However, treating this process as a fictitious equilibrium is equivalent to going through a series of more chemically realistic exchange steps and mathematically much simpler to deal with. 

While the redox chemistry of metal- and flavin-based cofactors may be readily detected by voltammetry, that associated with thiol-disulfides and amino acids is not. It is also important to be aware that voltammetry by itself provides no direct insight into the chemical identity of the redox couple. This can be overcome by using electrodes that allow for simultaneous spectroscopic and voltammetric analysis of adsorbed proteins. Examples include Ag electrodes that allow for surface-enhanced resonance Raman spectroscopy (SERRS) and mesoporous nanocrystalline Sn02 electrodes that allow for electronic absorption or magnetic circular dichro-ism spectroscopies [3]. Another consideration is the need for a redox center to be positioned within ca. 14 A of the electrode, and so the surface of the protein, for facile interfacial electron exchange. As a consequence, proteins with only buried redox centers are not routinely addressed by direct electrochemical methods. 

Combining atom transfer radical polymerization and disulfide/thiol redox chemistry a route to well-defined... 

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