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Using X-ray structure-based de novo design, a new class of inhibitors of the zinc-dependent endopeptidase Neprilysin has been developed that feature binding affinities (IC50 values) in the upper nanomolar range. The imidazole moieties of the central benzimidazole or imidazo[4,5-c]pyridine (see picture) scaffolds act as efficient peptide-bond isosters.
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Sahli et al. (2004) studied this question.
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