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Engineering novel protein-ligand interactions

Reference	B19078
Principal Investigator / Supervisor	Professor Stephen Caddick
Co-Investigators / Co-Supervisors	Professor Dek Woolfson
Institution	University College London
Department	Chemistry
Funding type	Research
Value (£)	184,144
Status	Completed
Type	Research Grant
Start date	01/01/2004
End date	31/12/2006
Duration	36 months

Abstract

Neocarzinostatin (NCS) is a clinically used natural complex from Streptomyces. NCS comprises a chromophore ligand (NCSchrom) non-covalently bound to a protein (apoNCS). NCSchrom is unstable and highly cytotoxic causing DNA damage. ApoNCS chaperones NCSchrom stabilising it and facilitating its delivery to cells. We have cloned and over-expressed apoNCS, and prepared simplified synthetic analogues of NCSchrom. We have used fluorescence and NMR spectroscopy to study the binding of the small molecules to apoNCS. We propose to build upon and exploit this base. Specifically, we will combine chemical and protein engineering to develop a novel system to allow the recruitment of a variety of pharmacophores to the binding pocket of apoNCS.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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