Preface [Hot Topic: Designing Targeted Libraries (Guest Editors: Guillermo A. Morales / Barry A. Bunin)]

摘要

This Combinatorial Chemistry and High-Throughput Screening compilation covers an array of diverse topics. The topics range from novel basic methods for synthesis, to gene-family targeted libraries, to pure design criteria, to dendrimers for gene delivery. New technologies discussed here, such as Microwave Chemistry and microreactors, as with the field of highthroughput chemistry, will establish their niches, becoming more widely used and eventually more cost-effective. The genefamily wide studies and design requirements span from focused libraries against specific targets to a general evaluation of Privileged Structures. In the design of libraries, researchers use creativity to identify novel chemotypes combined with balancing the desire for 'drug-like' compounds with synthetic accessibility. Everyone approaches the problems slightly differently, yet all are fighting one constant: we all have finite time for experimentation.nnThe common thread throughout all the studies is the search for greater efficiency using novel approaches to discover desired molecular properties. Spending 8 months to optimize a reaction to create a slightly more drug-like compound is as uneconomical as spending a single week making 80,000 highly impure compounds that contain functional group liabilities. Elegance in the fields of combinatorial chemistry and high-throughput screening is a combination of originality and efficiency in the design of compounds with desired profiles. Differences in approach are a function of the biological drug discovery screening environment for the overall efficiency of the portfolio of projects under consideration.nnGrander, increasingly ambitious themes are being addressed today than were ever previously attempted. Given the everexpanding number of research labs and publications, it becomes increasingly challenging to keep up with and build upon advances in a single field of interest, let alone peripheral fields that come into play when the truly grand questions are being asked. In response to this situation, collective efforts are beginning to emerge. One paper in this issue discusses the Membrane Protein Network (MePNet) program that deals with the pharmaceutically important mammalian GPCRs. In MePNet, three overexpression systems have been employed for the evaluation of 101 GPCRs, which has generated large quantities of numerous recombinant GPCRs, compatible for structural biology applications. As scientists start to work together on these broader projects for the common good, we will begin to see collective efforts in both Combinatorial Chemistry and High- Throughput Screening that resemble the collective efforts in the human genome sequencing projects and the emergence of both commercial and community databases for high-throughput drug discovery.