Chemistry Reference
In-Depth Information
combination of speed, miniaturization and ultimately the nature of the information sought
that drives the choice of analysis. With
in situ
medicinal chemistry, mass spectrometry
is without doubt the screening method of choice as it allows the rapid identification of
hit ligands from the complex reaction environment, with speed, sensitivity and minimal
sample cleanup or consumption required. The role of mass spectrometry in drug discovery
has changed dramatically; it is now a valued technique prominently integrated into drug
discovery settings rather than overlooked and placed in the obscurity of the basement.
Professor K. Barry Sharpless, Nobel Laureate for Chemistry (2001), has provided an
elegant description that captures the integral role of mass spectrometry leading to success
with
in situ
Click chemistry, and this sentiment is similarly valid for
in situ
DCC:
'This stealthy trickery would have been for naught but for the awesome POWER of modern
mass spectrometry to 'see' the tiny amount of triazole made 'accidentally'by the enzyme itself.
In effect the system found itself with the opportunity to shepherd a reaction step along that
meshed so perfectly that the new product fit its mould like a fine glove. Fitting so well in fact
the enzymes natural function was strongly interfered with.'
Personal communication, March 2007.
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