Hendrik M. Geysen, PhD

Hendrik M. Geysen, PhD

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Combinatorial chemistry. Synthesis, screening, analysis

A combinatorial approach to the synthesis of chemical libraries of small molecules for drug discovery, the rapid optimization of reaction sequences on solid-phase, and the identification of novel synthesis protocols.

Combinatorial chemistry, namely the use of automated synthesizers to carry out numerically large chemical operations, is a relatively recent discipline widely used by the pharmaceutical industry for the synthesis of large numbers of small molecules for screening against potential drug targets. A single library synthesis typically generates greater than 10,000 small molecules at a time, and takes only weeks to complete. The same technique has recently been used to optimize in a hereto-unprecedented manner several solid-phase reaction sequences. By carrying out in parallel 100's to 1000's of the same reaction sequence, varying the solvents, reagents, temperature and concentration, we are able to do more comprehensively in weeks what often takes 6-9 months by traditional methods. In the same way, by systematically interacting together many permutations of different functional groups under a large variety of chemical conditions, novel chemistries have been identified. To achieve these orders of magnitude increase in throughput, we rely heavily on designing creative experimental procedures, computerized robotics, and software algorithms for processing very large data sets. This laboratory's aims are to build on state-of-the-art technology developed in the pharmaceutical industry, novel enhanced combinatorial methods to address challenging problems in chemistry.