Sulfur protection with the 3‐nitro‐2‐pyridinesulfenyl group in solid‐phase peptide synthesis

Abstract

The 3-nitro-2-pyridinesulfenyl(Npys) group has been used successfully for side chain protection of cysteine during the stepwise solid-phase synthesis of Lys⁸-vasopressin(LVP) on benzhydrylamine resin. The versatility and limitations of this group have been evaluated by comparison of this synthesis with a parallel control synthesis using the 3,4-dimethylbenzyl(DMB) group and with a synthesis utilizing a combination of both groups. The Npys group was found to be stable to TFA as reported and, in addition, was found to be stable to HF:anisole(9:1) for 45 min at 0°, but not when thiol was present in either reagent. Furthermore, compatibility of the Npys group with the Boc-benzyl synthetic tactic in solid-phase peptide synthesis was demonstrated. LVP with full biological activity was obtained after purification by gel filtration and reverse-phase HPLC.