P-NITROBENZYL SIDE-CHAIN PROTECTION FOR SOLID-PHASE SYNTHESIS

A solid-phase supported peptide synthesis (SPPS) strategy using p-nitr obenzyl (pNB) esters thioethers and carbamates for side-chain protecti on is described. The synthesis of Fmoc p-nitrobenzyl side-chain protec ted amino acids of lysine, cysteine, glutamic acid and aspartic acid a re synthesized and incorporated into the synthesis of tetramers by sta ndard Fmoc methodology using Wang polystyrene resins. Deprotection is carried out on resin in mildly acidic reducing conditions, using a sol ution of DMF, SnCl2, phenol and HOAc. The yellow by-products associate d with the deprotection of the pNB protecting group are then removed b y treatment with a solution of benzene sulfinic acid in DMF. The metho dology is successfully extended in the synthesis of a peptide with mul tiple pNB protecting groups.