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Mechanistic and structural studies on nucleoside DNA glycoside hydrolases

Reference	BCI06200
Principal Investigator / Supervisor	Professor Michael Blackburn
Co-Investigators / Co-Supervisors	Professor David Hornby
Institution	University of Sheffield
Department	Chemistry
Funding type	Research
Value (£)	92,469
Status	Completed
Type	Research Grant
Start date	14/07/1996
End date	04/10/1998
Duration	27 months

Abstract

Cleavage of the glycosylic bond between deoxyribose and a modified base is the key to enzyme repair of DNA. Its mechanism will be explored for the enzyme uracil-DNA glycosylase, UDGase. Alternative mechanisms of hydrolysis, SN2 displacement by water and SN1 ionisation involving C1'- carbocation stabilisation, will be differentiated by the use of two alternative types of substrate. 4'-Carbadeoxynucleosides will be used in kinetic, equilibrium, and structural studies as inhibitors of SN1 but not SN2 processes. C-Nucleosides, especially 2'-deoxypseudouridine, will block cleavage by either mechanism. These will be incorporated into single-strand trimers and double strand dodecamers to be used in binding and crystallisation studies on UDGase.

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	Biological Chemistry Initiative (BCI) [1995]
Funding Scheme	X – not Funded via a specific Funding Scheme

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