A gene-expression inhibitor that targets an α-helix-mediated protein interaction

Journal of the American Chemical Society

Volumn 125, Issue 17, 2003, Pages 4992-4993

  Asada, Shinichi ^a   Choi, Yongmun ^a   Uesugi, Motonari ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADAMANOLOL; INDOLE DERIVATIVE; PINDOLOL; UNCLASSIFIED DRUG;

ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CONTROLLED STUDY; DRUG TARGETING; EMBRYO; GENE EXPRESSION REGULATION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; ONCOGENE NEU; PROTEIN PROTEIN INTERACTION; TRANSCRIPTION INITIATION;

EID: 0037473529     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja0292703     Document Type: Article

References (15)

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10. Poor cell-permeability is often a problem of inhibitors of protein-protein interactions. In our study, we performed cell-based screens to eliminate non-cell-permeable molecules. Details of the cell-based screens are shown in the Supporting Information.
11. The activation domains of VP16 and NF-κB p65 served as an excellent control because both have been reported to be α helical [Uesugi, M.; Nyanguile, O.; Lu, H.; Levine, A. J.; Verdine, G. L. Science 1997, 277, 1310-1313. Schmitz, M. L.; Silva, M. A.; Altman, H.; Czisch, M.; Holak, T. A.; Baeuerle, P. A. J. Biol. Chem. 1994, 269, 25613-256201 and are as potent as ESX is in cells. However, it is possible that adamanolol is not completely specific for the ESX activation domain.
12. The activation domains of VP16 and NF-κB p65 served as an excellent control because both have been reported to be α helical [Uesugi, M.; Nyanguile, O.; Lu, H.; Levine, A. J.; Verdine, G. L. Science 1997, 277, 1310-1313. Schmitz, M. L.; Silva, M. A.; Altman, H.; Czisch, M.; Holak, T. A.; Baeuerle, P. A. J. Biol. Chem. 1994, 269, 25613-256201 and are as potent as ESX is in cells. However, it is possible that adamanolol is not completely specific for the ESX activation domain.
13. 129-145 for Sur-2 was 12 μM under the same condition (Figure S1).
14. Complete assignments of the proton signals of adamanolol were achieved through TOCSY, DQF-COSY, and NOESY experiments. A summary of key NOE connectivities is shown in Figure S2.
15. A less constrained adamanol derivative that lacks the isopropyl group had no detectable activity in SK-BR3 cells even at 100 μM, supporting the notion that the Z conformation is important for the activity (Uesugi, M.; Shimogawa, H.; Kigoshi, H., unpublished results).