MARCY · Structural effects arising from major groove dna recognition by metallo-supramolecular cylinders

Lines connect the coordinator with its partners.

Project objective

The objective is to investigate the binding of metallo-supramolecular cylinders to DNA and to probe the remarkable structural effects induced by these cylindrical units with the goal of deliberately achieving such effects in a sequence-specific fashion. While DNA encodes the essential blueprint for life, within biological systems its structure and function is regulated by proteins. In the post genomic environment the goal is to understand the processing of the genetic code and how to stimulate or prevent this. Proteins frequently achieve DNA recognition via binding in or around its major groove since the size and shape of the major groove of B-DNA varies most with base sequence. Small synthetic recognition agents tend to target the minor groove or act via intercalation and often cause little or no bending of the DNA. Synthetic agents that target the major groove of DNA with recognition through non-covalent surface motifs have the potential to be a powerful new tool in the armoury of reagents that is being developed to tackle the post genomic challenge. Little progress has been made in this direction, due in large part to the size of the molecular surfaces required to achieve this. Supramolecular chemistry permits the design of large synthetic arrays, bridging the size-gap between small molecule and larger biomolecule DNA recognition-motifs. 3 partners in this proposal have described the DNA binding of a tetracationic supramolecular cylinder that is just the right size to fit into the major groove of DNA and too big for the minor groove (Angew. Chem., Intl. Ed., 2001, 40, 879-4). Excitingly this major groove-binding cylinder also induces a dramatic intramolecular bending effect resulting in coils of DNA that is unprecedented with a synthetic DNA binder. This proposal will develop and exploit these important findings. We will design and prepare synthetic metallo- supramolecular cylindrical major-groove recognition agents. We will investigate their

Original text from CORDIS.

Participants

• UNIVERSITY OF WARWICK · COVENTRYCoordinatorUnited Kingdom
• CHALMERS UNIVERSITY OF TECHNOLOGY · GOETEBORGSweden
• CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS · MADRIDSpain
• INSTITUTE OF BIOPHYSICS - ACADEMY OF SCIENCES OF THE CZECH REPUBLIC · BRNOCzechia
• UNIVERSITAT DE BARCELONA · BARCELONASpain

Links

• View on CORDIS