New disulfide reducing reagent for solid phase peptide synthesis.
Mthembu, Sinenhlanhla Nonhlanzeko.
MetadataShow full item record
The special physical and chemical properties of sulfur atom make thiols and disulphide bonds of vital importance in many biological processes. For instance, it is well known, the role of cysteine residues in proteins, acting as key in the catalytic site of enzymes or stabilizing the tertiary structure of proteins through disulfide bonds. In nature, glutathione is responsible for reducing disulphide bonds formed within the cytoplasmic proteins to cysteines. To mimic this function on the bench, many disulfide reducing agents have been developed. β-mercaptoethanol (β-ME) and dithiothreitol (DTT) work in a similar manner as GSH except that DTT forms intramolecular disulphide bond yielding a very stable six-membered ring, making DTT a more effective reducing agent. Recently, a new reducing agent inspired in DTT was developed from aspartic acid, Dithiobutylamine (DTBA), which work faster and because its lower thiol pKa value, showed a good reactivity at physiological pH. Due to the high polarity of DTBA, it is only soluble in aqueous solution, thus in this work, a non-polar analogue 2-(dibenzylamino)butane-1,4-dithiol (DABDT) has been developed. The molecule has been successfully obtained in good yield by a five-step process as an almost odorless solid. In solution, DABDT has good stability and its performance as reducing agent is comparable to DTT. Moreover, its efficacy has been probed as reducing agent of disulfide protected Cys and thiol derivatized peptide on solid phase.