3-Nitro-2-Pyridinesulfenyl Group for Protection and Activation of the Thiol Function of Cysteine

Abstract

The use of the 3-nitro-2-pyridinesulfenyl (Npys) halide, a versatile reagent in peptide chemistry, for the protection and activation of the thiol function is reported. Boc-Cys(Npys)–OH is prepared starting from bis(N-t-butyloxycarbonyl)-l-cystine. The Npys group is easily removed by treatment with a stoichiometric amount of tri-n-butylphosphine in the presence of water, but it is resistant to acids such as trifluoroacetic acid, HCl, and HF. Importantly, the cysteine residue modified with the Npys group can react selectively with free thiol of cysteine to afford a cystine disulfide bond.

Amino Acid-Protecting Groups

“…It is removed by reducing thiols and phosphines to render the free thiol. 368 It is stable to TFA and HF but it is not stable to the low-high cleavage protocol or to bases. 369 It is used in the Boc/Bn strategy mainly to obtain disulfide bonds by nucleophilic displacement by the thiol of a free Cys.…”

Methods for the Peptide Synthesis and Analysis

“…This protecting group has been widely used in the formation of disulfide bridges in solid-phase [58]. S-tert-butyl (StBu) (31) [59] and S-3-nitro-2-pyridine-sulfenyl (S-Npys) (32) [60] groups can be removed by thiolysis. S-Npys group is not stable toward piperidine treatment and thus needs to be used in Boc chemistry strategies or introduced as Boc-Cys(Npys)-OH residue at the N-terminal position when using Fmoc approaches.…”

Synthetic Approaches for Total Chemical Synthesis of Proteins and Protein-Like Macromolecules of Branched Architecture

“…The thiol chemistry was extensively used in the preparation of macromolecules with thioether and disulfide ligation sites [160][161][162][163][164][165][166][167][168][169][170]. Usually a thiol such as Cys reacts with an N-terminal chloro-or bromo-acetyl peptide to generate the thioether bond (Fig.…”