Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis |
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Authors: | A Bhandari DG Jones JR Schullek K Vo CA Schunk LL Tamanaha D Chen Z Yuan MC Needels MA Gallop |
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Affiliation: | Affymax Research Institute, Palo Alto, CA 94304, USA. |
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Abstract: | Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049. |
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