This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent advances in the ability to monitor activation and repression of gene activity ('gene chip' technology) have opened the possibility of studying the activity of drugs at the level of global effects upon gene transcription rather than the level of activity against isolated proteins. This type of monitoring has the potential to reveal important information about drug resistance mechanisms and modes of activity that are otherwise unavailable. As a test-bed for developing such methods, we have chosen to explore the structure activity relationship of the benzimidazole fungicides towards the gene expression patterns of brewer's yeast (S. cerevisiae). We have approached the project by synthesizing a position-indexed library of these fungicides, treating yeast, and correlating the patterns of gene activity with primary drug structure. One particularly facile method for characterization of the structure and purity of these library members (generally of 200 - 300 MW) is by fragmentation analysis from EI mass spectrometry. When coupled with gas chromatography, this approach has the potential to provide information about both the purity of individual library members and their identity.
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