Submitted by mam2155 on March 24, 2014 - 4:19pm
| Title | N,C-Capped dipeptides with selectivity for mycobacterial proteasome over human proteasomes: role of S3 and S1 binding pockets. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Lin G, Chidawanyika T, Tsu C, Warrier T, Vaubourgeix J, Blackburn C, Gigstad K, Sintchak M, Dick L, Nathan C |
| Journal | J Am Chem Soc |
| Volume | 135 |
| Issue | 27 |
| Pagination | 9968-71 |
| Date Published | 2013 Jul 10 |
| ISSN | 1520-5126 |
| Keywords | Binding 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. |
| DOI | 10.1021/ja400021x |
| Alternate Journal | J. Am. Chem. Soc. |
| PubMed ID | 23782398 |
| PubMed Central ID | PMC3773049 |
| Grant List | 1R21AI101393 / 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 |