Topological Regulation of the Bioactive Conformation of a Disulfide-Rich Peptide, Heat-Stable Enterotoxin
Heat-stable enterotoxin (ST ) produced by enterotoxigenic causes acute diarrhea and also can be used as a specific probe for colorectal cancer cells. ST contains three intra-molecular disulfide bonds (C1-C4, C2-C5, and C3-C6 connectivity). The chemical synthesis of ST provided not only the native ty...
Gespeichert in:
Veröffentlicht in: | Molecules (Basel, Switzerland) Switzerland), 2020-10, Vol.25 (20), p.4798 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Heat-stable enterotoxin (ST
) produced by enterotoxigenic
causes acute diarrhea and also can be used as a specific probe for colorectal cancer cells. ST
contains three intra-molecular disulfide bonds (C1-C4, C2-C5, and C3-C6 connectivity). The chemical synthesis of ST
provided not only the native type of ST
but also a topological isomer that had the native disulfide pairings. Interestingly, the activity of the topological isomer was approximately 1/10-1/2 that of the native ST
. To further investigate the bioactive conformation of this molecule and the regulation of disulfide-coupled folding during its chemical syntheses, we examined the folding mechanism of ST
that occurs during its chemical synthesis. The folding intermediate of ST
with two disulfide bonds (C1-C4 and C3-C6) and two Cys(Acm) residues, the precursor peptide, was treated with iodine to produce a third disulfide bond under several conditions. The topological isomer was predominantly produced under all conditions tested, along with trace amounts of the native type of ST
. In addition, NMR measurements indicated that the topological isomer has a left-handed spiral structure similar to that of the precursor peptide, while the native type of ST
had a right-handed spiral structure. These results indicate that the order of the regioselective formation of disulfide bonds is important for the regulation of the final conformation of disulfide-rich peptides in chemical synthesis. |
---|---|
ISSN: | 1420-3049 1420-3049 |
DOI: | 10.3390/molecules25204798 |