ABSTRACT
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.
Subject(s)
Indigo Carmine/analogs & derivatives , Peptides/chemical synthesis , Cysteine/chemistry , Indigo Carmine/chemistry , Peptides/chemistry , Phosphines/chemistryABSTRACT
This Minireview focuses on the hemithioindigo photoswitch and its use for the reversible control of three-dimensional peptide structure and related biological functions. Both the general design aspects and biophysical properties of various hemithioindigo-based chromopeptides are summarized. Hemithioindigo undergoes reversible ZâE photoisomerization after absorption of visible light. The unique ultrafast switching mechanism of hemithioindigo combines picosecond isomerization kinetics with strong double-bond torsion after light absorption, making it the ideal tool for instantaneous modulation of biological structure. Various inhibitors and model peptides based on hemithioindigo are described that can directly regulate biological signaling or allow the fastest events in peptide folding to be studied. Finally, a diverse range of chromopeptides with photoswitchable ß-hairpin structures based on azobenzenes, stilbenes, and hemithioindigo are compared to emphasize the unique properties of hemithioindigo.
