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

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• 作者：Jitendra R. Harjani ; Beow Keat Yap ; Raymond S. Norton ; Jonathan B. Baell ; ^{Jonathan.Baell@monash.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cystathionine ; Cyclopeptides ; SPSB2-iNOS
• 刊名：Tetrahedron
• 出版年：2016
• 出版时间：9 June 2016
• 年：2016
• 卷：72
• 期：23
• 页码：3256-3261
• 全文大小：561 K

文摘

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.