A potent, versatile disulfide-reducing agent from aspartic acid.

Journal of the American Chemical Society
John C LukeshRonald T Raines

Abstract

Dithiothreitol (DTT) is the standard reagent for reducing disulfide bonds between and within biological molecules. At neutral pH, however, >99% of DTT thiol groups are protonated and thus unreactive. Herein, we report on (2S)-2-amino-1,4-dimercaptobutane (dithiobutylamine or DTBA), a dithiol that can be synthesized from l-aspartic acid in a few high-yielding steps that are amenable to a large-scale process. DTBA has thiol pK(a) values that are ~1 unit lower than those of DTT and forms a disulfide with a similar E°' value. DTBA reduces disulfide bonds in both small molecules and proteins faster than does DTT. The amino group of DTBA enables its isolation by cation-exchange and facilitates its conjugation. These attributes indicate that DTBA is a superior reagent for reducing disulfide bonds in aqueous solution.

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Citations

Jan 26, 2013·Molecular Pharmacology·Haoming ZhangPaul F Hollenberg
Sep 26, 2015·Journal of Pharmaceutical and Biomedical Analysis·Tao ChenColin D Medley
Apr 10, 2013·Biochimica Et Biophysica Acta·Jakob R Winther, Colin Thorpe
Apr 22, 2015·Nucleic Acids Research·Brian R FritzMichael C Jewett
Aug 16, 2016·The Journal of Reproduction and Development·Tayita SuttirojpattanaMasaya Geshi
Jan 22, 2015·PloS One·Sean B Johnston, Ronald T Raines
Mar 2, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kenta AraiMichio Iwaoka
Jan 15, 2017·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Mária Budai-SzűcsErzsébet Csányi
Jan 30, 2016·Chemical Communications : Chem Comm·Post Sai Reddy, Norman Metanis
Oct 15, 2013·Angewandte Chemie·John C LukeshRonald T Raines
Aug 25, 2017·Molecular Microbiology·Gustavo A AfanadorSean T Prigge
Oct 1, 2014·Organic & Biomolecular Chemistry·John C LukeshRonald T Raines
Mar 21, 2020·Chembiochem : a European Journal of Chemical Biology·Sinenhlanhla N MthembuBeatriz G de la Torre
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Dec 3, 2017·Chembiochem : a European Journal of Chemical Biology·Kenta AraiMichio Iwaoka
Jun 21, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Mengyun ZhouMeiqin Zhang
Feb 11, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shunsuke OkadaTakahiro Muraoka
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May 23, 2020·Analytical Chemistry·Malin KällstenSara Bergström Lind
Feb 7, 2018·Journal of the American Chemical Society·Jonathan P WojciechowskiPall Thordarson

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