Rationalising the inhibition of M. tuberculosis MshB by a series of inhibitors constructed from plumbagin conjugated via a viariable alkyl linker to a phenyl thioglycoside

Infection by M. tuberculosis results in an estimated 1.7 million TB related deaths worldwide. Mycothiol is produced in M. tuberculosis as the dominant low molecular weight thiol and is thought to protect the bacteria against oxidative stress. Since mycothiol is unique to Actinomycetes and is also proposed to play an important role in the dormant state of Mycobacteria, the pseudo-dissacharide is seen as a potential target for novel anti-tuberculars. Targeting the mycothiol redox cycle has led to MshB inhibition by a series of substrate analogues. Kinetics studied showed that the competitive inhibition increased when the alkyl linker was lengthened. The binding of the inhibitors was investigated using computational techniques in order to rationalise the observed trend in inhibition.

Grantor dc:publisher.institution

Department of Chemistry

Year dc:date.issued

2011

Author dc:creator

• Rogers, Ian L

Advisor dc:contributor.advisor

• Naidoo, Kevin J

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/11506

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/11506