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N,C-Capped dipeptides with selectivity for mycobacterial proteasome over human proteasomes: role of S3 and S1 binding pockets.

ABSTRACT: 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.

SUBMITTER: Lin G 

PROVIDER: S-EPMC3773049 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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N,C-Capped dipeptides with selectivity for mycobacterial proteasome over human proteasomes: role of S3 and S1 binding pockets.

Lin Gang G   Chidawanyika Tamutenda T   Tsu Christopher C   Warrier Thulasi T   Vaubourgeix Julien J   Blackburn Christopher C   Gigstad Kenneth K   Sintchak Michael M   Dick Lawrence L   Nathan Carl C  

Journal of the American Chemical Society 20130625 27

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. ...[more]

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