Fig. 13.

Chemical probes for trapping the ACP-KS interaction. A. Schematic representation of the chain extending reaction catalyzed by the KS domain illustrating interactions with upstream (yellow) or downstream (orange) ACP domain. B. Strategy for trapping the KS with the upstream ACP using epoxide- or β-chloroacrylate-functionalized pantetheine analogs. C. Probes 40, 41, and 42 used to produce derivatives loaded on the ACP. D. Synthesis of pantetheine analogs, which were subsequently converted to 40 and 41 with CoA biosynthetic enzymes, enabled production of crypto-ACPs. Synthesis of the Z-configured analog (not shown) coupled cis-3-chloroacrylic acid to the amine.