ortho- and meta-substituted aromatic thiols are efficient redox buffers that increase the folding rate of a disulfide-containing protein

Journal of Biotechnology
Jonathan D GoughWatson J Lees

Abstract

Thiol based redox buffers are used to enhance the folding rates of disulfide-containing proteins in vitro. Traditionally, small molecule aliphatic thiols such as glutathione are employed. Recently, we have demonstrated that aromatic thiols can further enhance protein-folding rates. In the presence of para-substituted aromatic thiols the folding rate of a disulfide-containing protein was increased by 4-23 times over that measured for glutathione. However, several important practical issues remain to be addressed. Aromatic thiols have never been tested in the presence of denaturants such as guanidine hydrochloride. Only two of the para-substituted aromatic thiols previously examined are commercially available. To expand the number of aromatic thiols for protein folding, several commercially available meta- and ortho-substituted aromatic thiols were studied. Furthermore, an ortho-substituted aromatic thiol, easily obtained from inexpensive starting materials, was investigated. Folding rates of scrambled ribonuclease A at pH 6.0, 7.0 and 7.7, with ortho- and meta-substituted aromatic thiols, were up to 10 times greater than those with glutathione. In the presence of the common denaturant guanidine hydrochloride (0.5M) aromatic thio...Continue Reading

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Oct 8, 2003·Biochemistry·Jonathan D GoughWatson J Lees
Jan 25, 2005·Bioorganic & Medicinal Chemistry Letters·Jonathan D Gough, Watson J Lees

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Citations

Nov 30, 2007·Biophysical Chemistry·Matthew FinkMahesh Narayan
May 19, 2012·The FEBS Journal·Mahesh Narayan
Oct 26, 2007·Biochemical and Biophysical Research Communications·Gabriel GomezMahesh Narayan
Jul 1, 2008·Annual Review of Cell and Developmental Biology·Bharath S Mamathambika, James C Bardwell
Dec 11, 2007·Bioorganic & Medicinal Chemistry·Minakshi C Gurbhele-TupkarWatson J Lees
Oct 1, 2014·Organic & Biomolecular Chemistry·John C LukeshRonald T Raines
Jan 31, 2009·Angewandte Chemie·Christian PiontekCarlo Unverzagt
Dec 27, 2011·Bioorganic & Medicinal Chemistry·Amar S Patel, Watson J Lees

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