Synthesis of de novo designed small-molecule inhibitors of bacterial RNA polymerase

摘要

The de novo molecular design program SPROUT has been used in conjunction with the X-ray crystal structure of RNA polymerase (RNAP) from Thermos aquaticus to produce a novel enzyme inhibitor scaffold. A short and efficient synthesis of molecules corresponding to this scaffold has been developed and in keeping with the design predictions, the resulting inhibitors displayed useful levels of inhibition of Escherichia coli RNAP. (C) 2008 Elsevier Ltd. All rights reserved.