Design and synthesis of new thiazolated cross-linked DNA binding polyamides for altered sequence recognition

The design and synthesis are described for six new thiazolated versions of cross-linked polyamides (), in which the Th–Py–Py array of heterocycles is tethered from the central pyrrole by C5 and C7 methylene chains. The thiazole ring in the different cross-linked polyamides () bears three different functional groups (viz. H, NHCHO and NH2). These six cross-linked polyamides were analyzed for their gyrase inhibition properties, which showed that amTh–Py–Py (), tethered by a C7 linker, with an inhibitory concentration against gyrase of (IC50=0.01 μM) is the most potent inhibitor among all the thiazolated cross-linked polyamides analyzed so far.