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Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure–activity relationship and pharmacophore modeling

Acta Cryst. (2012). D68, 511-520 (

[BoNT] Crystal structures of peptide inhibitors with BoNT/A. A close-up view of the BoNT/A active site with peptides is shown.

Botulinum neurotoxin (BoNT) is one of the most poisonous biological substances known to humans, with no drugs available on the market today for post-intoxication treatment. Efforts continue, as illustrated by Kumar et al., to develop inhibitors against the BoNT protease activity that disrupts the SNARE assembly and thus the release of neurotransmitters at neuromuscular junctions. They designed and tested a number of peptide inhibitors against the toxic action. The article illustrates the key pharmacophore features using the high-resolution crystal structures of a few peptide–BoNT complexes.

G. Kumar, D. Kumaran, S. A. Ahmed and S. Swaminathan