Alpha activity, early work

Early work with zinc metalloprotease inhibitors focused on the well-characterized agents captopril ((2S)-l-[(2S)-2-methyl-3-sulfanyl-propanoyl] pyrrolidine-2-carboxylic acid) and phos-phoramidon (/V-alpha-i,-rhamnopyranosyloxy[hydroxyphosphinyl -i,-leucyl-L-tryptophan). These compounds, however, were found to have little inhibitory activity against BoNT (Adler et al., 1994, 1999a). The poor efficacy of captopril was suggested to stem from unfavorable steric constraints in the binding of proline at the active site of BoNT (Schmidt and Stafford, 2002). 

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