Synthesis of peptide substrates for porcine elastase via (4-hydroxy-3-nitro)benzylated polystyrene (PHNB)

Abstract

Peptide synthesis by means of polymeric active esters was introduced recently as a new approach to the preparation of pcptides with a predetermined sequence [ 1,2] . In this technique amino acids or peptide esters possessing a free a-amino group are coupled with high molecular weight insoluble active esters of N-blocked amino acids and cross-linked hydroxyl polymers. The Nand D-blocked peptides obtained in such a reaction could be separated readily from the insoluble reagent and subsequently elongated by removal of the N-blocking group and by coupling with the insoluble polyfunctional active ester of a desired N-blocked amino acid. Although the successful preparation of several peptides was reported [ 1,2] we did not utilize the above approach routinely, as there were certain drawbacks in the physical and chemical properties of the polymeric active esters used [3]. As shown in our previous publication [4] , these difficulties were overcome by the use of (4-hydroxyl-3-nitro)benzylated polystyrene (PHNB). In this paper we describe further applications of PHNB active esters in the synthesis of several penta-, hexaand heptapeptides, designed as substrates for mapping the active site of porcine elastase [S-7] .