2,2′-Dithiobis(5-nitropyridine) (DTNP) as an effective and gentle deprotectant for common cysteine protecting groups
Article first published online: 14 NOV 2011
Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 18, Issue 1, pages 1–9, January 2012
How to Cite
Schroll, A. L., Hondal, R. J. and Flemer, S. (2012), 2,2′-Dithiobis(5-nitropyridine) (DTNP) as an effective and gentle deprotectant for common cysteine protecting groups. J. Peptide Sci., 18: 1–9. doi: 10.1002/psc.1403
- Issue published online: 26 DEC 2011
- Article first published online: 14 NOV 2011
- Manuscript Accepted: 29 JUN 2011
- Manuscript Revised: 21 JUN 2011
- Manuscript Received: 21 MAR 2011
- protecting group;
Of all the commercially available amino acid derivatives for solid phase peptide synthesis, none has a greater abundance of side-chain protection diversity than cysteine. The high reactivity of the cysteine thiol necessitates its attenuation during peptide construction. Moreover, the propensity of cysteine residues within a peptide or protein sequence to form disulfide connectivity allows the opportunity for the peptide chemist to install these disulfides iteratively as a post-synthetic manipulation through the judicious placement of orthogonal pairs of cysteine S-protection within the peptide's architecture. It is important to continuously discover new vectors of deprotection for these different blocking protocols in order to achieve the highest degree of orthogonality between the removal of one species in the presence of another. We report here a complete investigation of the scope and limitations of the deprotective potential of 2,2′-dithiobis(5-nitropyridine) (DTNP) on a selection of commercially available Cys S-protecting groups. The gentle conditions of DTNP in a TFA solvent system show a remarkable ability to deprotect some cysteine blocking functionality traditionally removable only by more harsh or forcing conditions. Beyond illustrating the deprotective ability of this reagent cocktail within a cysteine-containing peptide sequence, the utility of this method was further demonstrated through iterative disulfide formation in oxytocin and apamin test peptides. It is shown that this methodology has high potential as a stand-alone cysteine deprotection technique or in further manipulation of disulfide architecture within a more complex cysteine-containing peptide template. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.