LabAutomation 2006 - SLAS

LabAutomation2006
12:00 pm Monday, January 23, 2006 Track 3: High-Throughput Technologies Room: Learning Center
Wyndham Palm Springs Hotel
Paul Watts
University of Hull
Hull, United Kingdom
p.watts@hull.ac.uk
High-Throughput Synthesis of Analytically Pure Compounds Within Flow Reactors
The miniaturisation of chemical reactors offers many fundamental and practical advantages of relevance to the chemical industry, who are
constantly searching for controllable, information rich, high throughput, environmentally friendly methods of producing products with a high
degree of chemical selectivity.
In this presentation a number of chemical reactions of industrial interest will be used to illustrate the advantages that micro reactors offer
for the rapid optimisation of reactions, in which the product is typically produced in both higher yield and purity. It will be illustrated that
compounds may be prepared and purified within an integrated system and that it is possible to generate intermediates in situ within the
reactor, which may then be subsequently reacted to produce more complex products. More recently the incorporation of solid supported
reagents and catalysts has been investigated and the results will be discussed. The use of solid supported reagents adds even greater
diversity to the range of reactions that may be achieved within such systems. It will be demonstrated that the dimensions of reactors may
be increased in size while maintaining the classic advantages associated with miniaturisation. In such systems significant quantities of
analytically pure compound may be prepared without additional purification. Furthermore, integration of the microfluidic system with realtime
analytical detection will be illustrated enabling in situ process control to be achieved.
3:00 pm Monday, January 23, 2006 Track 3: High-Throughput Technologies Room: Learning Center
Wyndham Palm Springs Hotel
Joshua Salafsky
Biodesy, LLC
Burlingame, California
salafsky@biodesy.com
Detection of Protein Conformational Change in Real-Time with Second-Harmonic
Generation
In this talk, I will show that optical second-harmonic generation (SHG), a nonlinear optical technique, can be adapted to be a unique probe
of conformational change in proteins and other biomolecules. In conjunction with second-harmonic-active labels (‘SHG-labels’) and other
methods pioneered by Biodesy LLC, proteins are easily detectable on a chip surface. SHG is an intrinsically surface-sensitive technique
that excludes all isotropic background sources, so less than a monolayer of protein molecules is necessary for detection with a good
signal-to-noise ratio. Our technology is highly sensitive to small structural shifts in a protein, making it an excellent means of detecting
ligand- or drug-induced conformational change. We expect this approach to become an important advance in high-throughput drug
discovery, as well as basic research, and to provide a dynamic picture of the protein-drug interaction at unprecedented resolution.
A number of drug discovery applications are now within reach, including the rapid discovery of conformation-selective drugs for kinases
or integrins, important targets for cancers and inflammation, and the discovery of inhibitors of ‘misfolding’ amyloidogenic proteins such as
β-amyloid and α-synuclein, common targets for Alzheimer’s and Parkinson’s diseases. Screening of allosteric modulators is enabled via
direct detection of the magnitude or angular-dependence of conformational change in a protein molecule. Detection of DNA hybridization
on a chip without the need for labeling probe strands or stringent washes, potentially suitable for clinical diagnostics or point-of-care
detection, is another attractive application.
In addition to providing real-time, structural information, SHG technology is well suited to high-throughput scale-up, as the second-harmonic
emission is collimated and easily separable (spectrally) from the fundamental beam.
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