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We identified N,C-capped dipeptides that are selective for the Mycobacterium tuberculosis proteasome over human constitutive and immunoproteasomes. Differences in the S3 and S1 binding pockets appeared to account for the species selectivity. The inhibitors can penetrate mycobacteria and kill nonreplicating M. tuberculosis under nitrosative stress.

N,C-Capped Dipeptides with Selectivity for Mycobacterial Proteasome over Human Proteasomes: Role of S3 and S1 Binding Pockets