Drug discovery and vaccine development using mixture-based synthetic combinatorial libraries.
The approaches and concepts that encompass combinatorial chemistry represent a paradigm shift in drug discovery and basic research. Viewed initially as a curiosity by the pharmaceutical industry, combinatorial chemistry approaches are now recognized as essential drug discovery tools that decrease the time taken for discovery and increase the throughput of chemical screening by as much as 1000-fold. Although the use of mixture-based synthetic combinatorial libraries was one of the first approaches presented, its inherent strengths are only recently being recognized. Numerous mixture-based libraries of peptides, peptidomimetics and heterocycles have been synthesized and deconvoluted using the positional scanning approach. Mixture-based library approaches for drug discovery and vaccine development will be reviewed herein.
Houghten
RA
Mixture Sciences, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
Wilson
DB
Pinilla
C