omation mbers - Society for Laboratory Automation and Screening

TP058
Kirk Malone
The University of Edinburgh
The School of Chemistry
Joseph Black Building, West Mains Road
Edinburgh EH9 3JJ United Kingdom
Kirk.Malone@ed.ac.uk
The Design and Synthesis of High Affinity Ligands for Human Cyclophilin A
175
Co-Author(s)
Nicholas J. Turner
Malocolm Walkinshaw
Cyclophilin A (CypA) is a member of the immunophilin family of proteins and a receptor for the immunosuppressant
drug cyclosporin A (CsA). CypA also catalyses cis-trans isomerisation of peptidyl-prolyl (Xaa-Pro) amide bonds,
biologically important in protein folding. CypA is a potential therapeutic target for areas including HIV replication
and parasitic development. The use of a computational molecular docking programme to screen a virtual library
of compounds identified dimedone (5,5-dimethyl-1,3-cyclohexanedione) as a potential ligand. A number of low
molecular weight ligands have been synthesised based upon O-acylated dimedone and N-acylated aminodimedone.
Routes to 4-alkylated dimedone were also investigated and derivatives synthesised. Ligands were
screened for binding to CypA using mass spectrometry, and ligand:CypA complexes were observed under
electrospray ionisation conditions. Recent work has focused on the synthesis of a combinatorial library of
compounds to further investigate the ligand:protein interaction.
TP059
Justin Mecomber
University of Cincinnati
Department of Chemistry
404 Crosley Tower
Cincinnati, Ohio 45221-0172
mecombjs@email.uc.edu
Rapid and Cost-Effective Prototyping of Plastic Microfabricated Devices for Mass
Spectrometry
Co-Author(s)
Douglas Hurd
Patrick A. Limbach
The increased interest in polymer-based microfabricated and microfluidics devices as alternatives to silica-based
devices for bioanalysis that are generated by a molding process require the generation of metal molding masters.
Traditionally, expensive or time-consuming approaches including LIGA, UV-Lithography or electrical discharge
machining are used to generate metal molding masters. Here, we demonstrate that conventional CNC-mills, such
as those readily available in university or private machine shops, can be used to generate metal features with
tolerances up to a factor of 10 better than expected from the mill specifications. With such improved machining
tolerances, a CNC-milling approach can now be used to generate high aspect ratio features suitable for lab-ona-chip
devices. Hot embossing, in conjunction with solvent bonding, has been utilized to fabricate these polymer
devices. An electrophoresis based detection system using fluorescence microscopy has been employed to
determine the analytical capabilities of microchips generated in this manner. Comparisons with microchips made
by molding fabrication methods such as wire imprinting and LIGA will be compared to microchips produced from
the molds made by CNC-machining. These easily produced chips are of a suitable quality and design for use with
analytical methods such as microchip-CE laser induced fluorescence or mass spectrometry.
POSTER ABSTRACTS