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

TitleN,C-Capped dipeptides with selectivity for mycobacterial proteasome over human proteasomes: role of S3 and S1 binding pockets.
Publication TypeJournal Article
Year of Publication2013
AuthorsLin G, Chidawanyika T, Tsu C, Warrier T, Vaubourgeix J, Blackburn C, Gigstad K, Sintchak M, Dick L, Nathan C
JournalJ Am Chem Soc
Volume135
Issue27
Pagination9968-71
Date Published2013 Jul 10
ISSN1520-5126
KeywordsBinding Sites, Dipeptides, Dose-Response Relationship, Drug, Humans, Models, Molecular, Molecular Structure, Mycobacterium tuberculosis, Proteasome Endopeptidase Complex, Structure-Activity Relationship
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.

DOI10.1021/ja400021x
Alternate JournalJ. Am. Chem. Soc.
PubMed ID23782398
PubMed Central IDPMC3773049
Grant List1R21AI101393 / AI / NIAID NIH HHS / United States
R21 AI101393 / AI / NIAID NIH HHS / United States
R56 AI080618 / AI / NIAID NIH HHS / United States
R56AI080618 / AI / NIAID NIH HHS / United States

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