Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0740441 (
acute diarrhea
)
2,275
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Heat-stable enterotoxin (ST
a
) produced by enterotoxigenic
E. coli
causes
acute diarrhea
and also can be used as a specific probe for colorectal cancer cells. ST
a
contains three intra-molecular disulfide bonds (C1-C4, C2-C5, and C3-C6 connectivity). The chemical synthesis of ST
a
provided not only the native type of ST
a
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
a
. 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
a
that occurs during its chemical synthesis. The folding intermediate of ST
a
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
a
. 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
a
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.
...
PMID:Topological Regulation of the Bioactive Conformation of a Disulfide-Rich Peptide, Heat-Stable Enterotoxin. 3309 91
