Synthesis of hemithioindigo ‐based chromopeptides by using the Tmb auxiliary in native chemical ligation studies

The 4,5,6‐trimethoxy‐2‐mercaptobenzyl auxiliary was used in auxiliary‐based native chemical ligation reactions with Boc‐protected pHTI and mHTI ω‐amino acid thioesters 2a,b for the construction of small hemithioindigo (HTI)‐based chromopeptides 6a,b with a class 1 PDZ binding motif. While reversible tris(2‐carboxyethyl)phosphine (TCEP)‐HTI adduct formation required moderate use of access TCEP, the Na ascorbate concentration was broadly varied for optimization of the reaction conditions. In the studies presented, the mHTI ω‐amino acid thioester 2b proved to be slightly less reactive than the pHTI ω‐amino acid thioester 2a. Ligated products 5a–d were isolated in 35–81% yield, and also cleavage of the auxiliary proceeded smoothly, furnishing peptides 6a–d in 48–61% yield. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Thiol auxiliary (Tmb) mediated native chemical ligation with HTI ω‐amino acid thioesters in the presence of variable amounts of Na ascorbate, and TCEP has been applied for the synthesis of HTI chromopeptides. The ligation reactions are highly efficient in spite of reversible TCEP‐HTI adduct formation.
Source: Journal of Peptide Science - Category: Biochemistry Authors: Tags: Special Issue Article Source Type: research