An alternative approach to the synthesis of peptides containing a cystathionine bridge

• DOI: 10.1016/j.tet.2016.04.051
• Publication Date: 2016-04-30T21:55:01Z
• Authors: Jitendra R. Harjani; Beow Keat Yap; Raymond S. Norton; Jonathan B. Baell
• Keywords: 0301 basic medicine; 03 medical and health sciences

Abstract A new method for the synthesis of cystathionine containing cyclic peptides has been developed. Conventionally such systems are typically made with relatively late-stage on-resin cyclisation involving reaction between a chlorohomoalanine and cysteine residue. We offer a different approach involving early incorporation of a cystathionine residue through on-resin reaction between a cysteine residue and an N-Alloc iodohomoalanine cumyl ester. Subsequent cyclisation then involves amide bond formation. The success of this method was demonstrated by applying it to the synthesis of a cystathionine analogue of the disulfide bridge cyclic peptide, N-acetylated cyclic peptide c[CVDINNNC]-NH2, a biologically active iNOS binding epitope mimetic that binds tightly to the protein, SPSB2. Our method expands the repertoire of synthetic options towards the construction of cystathionine containing cyclic peptides.