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: EC:3.4.24.69 (
botulinum neurotoxin
)
1,901
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The peptide N-acetyl-CRATKML-amide is an effective inhibitor of type A
botulinum neurotoxin
(
BoNT
A) protease activity [
Schmidt
et al., FEBS Lett. 435 (1998) 61-64]. To improve inhibitor binding, the peptide was modified by replacing cysteine with other sulfhydryl-containing compounds. Ten peptides were synthesized. One peptide adapted the structure of captopril to the binding requirements of
BoNT
A, but it was a weak inhibitor, suggesting that angiotensin-converting enzyme is not a good model for
BoNT
A inhibitor development. However, replacing cysteine with 2-mercapto-3-phenylpropionyl yielded a peptide with K(i) of 330 nM, the best inhibitor of
BoNT
A protease activity reported to date. Additional modifications of the inhibitor revealed structural elements important for binding and supported our earlier findings that, with the exception of P1' arginine, subsites on
BoNT
A are not highly specific for particular amino acid side chains.
...
PMID:A high-affinity competitive inhibitor of type A botulinum neurotoxin protease activity. 1248 5
