Development of anti-sigma factor agents

Details Development of anti-sigma factor agents Development of anti-sigma factor agents

2006-02-07

2006-02-07

Leary, Louise N. (Department: 1654)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving viable micro-organism

C435S004000, C435S029000, C435S849000

Reexamination Certificate

active

06994985

ABSTRACT:
Sigma factors are a unique family of essential proteins found in bacterial, but not eukaryotic cells, which are responsible for recognition of promoter DNA and delivery of the catalytic domain of RNA polymerase to a gene signaled to be expressed. The present invention relates to methods for identifying agents that are capable of inhibiting bacterial gene expression via inhibition of sigma factor activity. In particular, the invention relates to the interaction of bacteriophage T4 AsiA protein and the C-terminal DNA binding domain of sigma factor (the SR4 domain) and the use of the structural information derived from this interaction to model, prepare and identify agents capable of binding and inhibiting sigma factor activity. Moreover, the invention relates to the design of AsiA mimics, including small organic molecules, peptides or proteins that binds SR4 and abrogates sigma factor activity, or screening for AsiA mimics that show bacteriostatic or bacteriocidal properties.

REFERENCES:
Lambert et al, EMBO J., Dec. 2001; V.20(24): p 7149-7159.
Guerra et al; Antimicrobial Agents & Chemotherapy, Apr. 2001, p. 1305-1308, V. 45(4).
Urbauer, Jeffrey L. et al. (2002) “Solution structure and stability of anti-sigma factor AsiA: Implications for novel functions” vol.: 99, No. 4, pp. 1831-1835.

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