Dithiothreitol (DTT) is the standard reagent used for the reduction of disulfide bonds in biological molecules. But with thiol pKa values of 9.2 and 10.1, the molecule is mostly inactive at neutral pH. Herein, we report on (2S)-2-amino-1,4-dimercaptobutane (dithiobutylamine or DTBA), a dithiol that is easily accessed from L-aspartic acid. DTBA possesses thiol pKa values that are approximately 1 unit lower than those of DTT and forms a similar six-membered dithiane ring upon oxidation. DTBA reduces disulfide bonds in both small molecules and proteins faster than does DTT. We also note that the amino group on DTBA facilitates its covalent attachment to a resin, surface, or soluble molecule. These attributes of DTBA could enable it to supplant DTT as the preferred reagent for reducing disulfide bonds in biomolecules.

Construction of a potent, versatile disulfide-reducing agent from aspartic acid

245th National Meeting (2013)

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