BIOL 70 |
| Carrier protein and coenzyme A mediated processes sit at the center of both primary and secondary metabolic pathways, functioning in the biosynthesis of fatty acids, polyketides, and nonribosomal peptides. A feature common to all these pathways is the utilization of 4'-phosphopantetheine arm and thioester linkage for the facile processing and cleavage of biosynthetic intermediates. Recently we demonstrated that synthetic analogues of pantetheine combined with purified CoA biosynthetic enzymes and the promiscuous phosphopantetheinyl transferase Sfp can be useful for in vitro labeling of carrier proteins with fluorescence or affinity tags, conformational locking of carrier protein with interacting domains, and in vivo metabolic labeling of acyl carrier proteins by co-opting of the endogenous biosynthetic pathway. Here we describe both large and small-scale syntheses and biological evaluation of a panel of pantetheine analogs incorporating bioorthogonal functionalities, affinity tags, and non-hydrolyzable substrate analogs for use as probes of CoA and carrier protein mediated processes. |
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Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |