p-Nitrobenzyl side-chain protection for solid-phase synthesis.

Abstract

A solid-phase supported peptide synthesis (SPPS) strategy using p-nitrobenzyl (pNB) esters, thioethers and carbamates for side-chain protection is described. The synthesis of Fmoc p-nitrobenzyl side-chain protected amino acids of lysine, cysteine, glutamic acid and aspartic acid are synthesized and incorporated into the synthesis of tetramers by standard Fmoc methodology using Wang polystyrene resins. Deprotection is carried out on resin in mildly acidic reducing conditions, using a solution of DMF, SnCl2, phenol and HOAc. The yellow by-products associated with the deprotection of the pNB protecting group are then removed by treatment with a solution of benzene sulfinic acid in DMF. The methodology is successfully extended in the synthesis of a peptide with multiple pNB protecting groups.