RATIONAL DESIGN OF ANTIBIOTICS TARGETED AT THE RIBOSOME

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43AI051104-01
Agency Tracking Number: AI051104
Amount: $225,000.00
Phase: Phase I
Program: SBIR
Awards Year: 2002
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
ANADYS PHARMACEUTICALS, INC.
ANADYS PHARMACEUTICALS, INC., 9050 CAMINO SANTA FE, SAN DIEGO, CA, 92121
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 THOMAS HERMANN
 (858) 530-3659
 THERMANN@ANADYSPHARMA.COM
Business Contact
 KLEANTHIS XANTHOPOULOS
Phone: (858) 530-3600
Email: KGX@ANADYSPHARAMA.COM
Research Institution
N/A
Abstract
Rapid and widespread emergence of antibiotic-resistant pathogens creates an urgent need for concerted approaches towards novel antibacterials. The long-term objective of this proposal is the development of synthetic antibiotics that overcome known resistance mechanisms. Structure-based molecular design in combination with leading-edge synthetic chemistry and screening methods will be used to exploit emerging structural data on the bacterial ribosome, a proven target for antibiotics. Selected natural antibiotics will serve as paradigms for the design of libraries consisting of novel aminoglycoside derivatives and thiopeptide mimetics. Crystal structures of the ribosomal target sites and computational analysis of their molecular recognition by ligands will aid the compound design effort. Compound libraries will be synthesized using convergent routes. Screening of compound libraries for their activity on the ribosomal target will be performed by fluorescence assays that have been developed for RNA targets at Anadys Pharmaceuticals. The integration of structure-based ligand design for the ribosome, one of the most complex macromolecular assemblies, with efficient synthesis of structurally complex ligands and their screening represents a formidable challenge. The benefit of the proposed research will extend beyond the immediate antibiotic discovery effort by providing the proof of principle for RNA as a feasible target for synthetic drugs. PROPOSED COMMERCIAL APPLICATIONS: The proposed research is aimed at discovering lead compounds that are potential antibiotics for the therapy of bacterial infections, especially for pathogens with resistance against existing antibiotics.

* information listed above is at the time of submission.

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