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Use of a crystal comprising DNA polymerase clamp factor for the conception of new antibiotics

Référence

85933-01

Statut des brevets

European patent EP03291596.9 filed on June 27, 2003, entitled “Protein crystal comprising the processivity clamp factor of DNA polymerase and a ligand, and its uses”

Inventeurs

Dominique BURNOUF
Jérôme WAGNER
Philippe DUMAS
Shingo FUJII
Robert FUCHS
Vincent OLIERIC

Statut commercial

Research agreement, exclusive or non exclusive licenses

Laboratoire

Laboratoire de Cancérogénèse et Mutagénèse Moléculaire Structurale (CMMS – UPR 9003), Strasbourg, France.

Description

TECHNICAL DESCRIPTION

A successful DNA replication process requires that the DNA polymerase becomes processive through its association, via a short peptide, with a processivity factor. A new approach is being developed to inhibit bacterial DNA replication by impeding this interaction. It relies on the co-crystallization of a complex containing the Escherichia coli processivity factor beta and the binding peptide from an E. coli DNA polymerase.
The present invention relates to the crystallization method, the crystal structure and the use of the atomic coordinates for the screening and the design of new antibacterial drugs.

Ref.: Structural and biochemical analysis of sliding clamp/ligand interactions suggest a competition between replicative and translesion DNA polymerases. Burnouf DY, Olieric V, Wagner J, Fujii S, Reinbolt J, Fuchs RP, Dumas P. J Mol Biol. 2004 Jan 30;335(5):1187-97.

INDUSTRIAL APPLICATIONS

This new approach in inhibiting bacterial DNA replication allows for the screening of new drugs for the treatment of bacterial diseases or diseases originating from DNA synthesis processes, such as fragile X syndrome, or proliferative disorders, such as cancers.

For further information, please contact us (Ref 85933-01)

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