(mentions CMT) From aphrodisiacs to designer inhibition

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From aphrodisiacs to designer inhibition

http://www.rsc.org/Publishing/ChemScience/Volume/2007/11/aphrodisiacs

_to_inhibition.asp

Ionic liquids can be designed to control protein activity, say

Australian researchers.

Adam McCluskey at the University of Newcastle, New South Wales,

Australia, and colleagues have found some of the most potent

inhibitors of dynamin, an enzyme with a range of biochemical roles.

'Almost weekly there are reports of dynamin mediated biological

effects, but as yet there are few chemical tools for studying it,

and even fewer agents that might have an effect on diseases related

to abnormal levels of dynamin expression or mutations,' said

McCluskey.

McCluskey's team made their ionic liquids by modifying cantharidin,

a compound secreted by the emerald green beetle known as the Spanish

fly. Cantharidin is purported to be an aphrodisiac, although even

relatively small doses can be fatal to humans.

'We can tune room temperature ionic liquids (RTILs) to interact with

proteins benignly via solvation and stabilisation, or as

inhibitors,' said McCluskey. Although the team had been

investigating the solvation of proteins, they were 'delighted' to

discover the inhibitory effects.

'The serendipitous outcome was new inhibitors of dynamin. Given the

increasing relevance of dynamin in human physiological conditions,

for example Charcot-Marie-Tooth, a common heredity disorder, this is

a significant advance,' explained McCluskey.

Nick Gathergood, a researcher in ionic liquids at Dublin City

University, Ireland, said the discovery of therapeutic properties of

these ionic liquids is a significant development. 'The work

illustrates an exciting interface of ionic liquid research with

medicinal chemistry. These novel materials have great potential,' he

added.

However, there is still plenty of work to be done. 'The lack of

predictability in the assembly of a cation and anion in the

generation of an RTIL is a major hurdle yet to be overcome,' said

McCluskey. He also cautioned that 'as these RTILs gain mainstream

acceptance we must examine their potential utility and potential

impact on biological systems'.