A fully automated solid-phase synthetic procedure for incorporation of positively charged guanidinium linkages into otherwise neutral PNA sequences has been employed. These DNG/PNA chimeras form [(DNG/PNA)(2). DNA] triplexes upon binding to single strand or duplex DNA (with accompanying D-loop for the latter). The [(DNG/PNA)(2) . DNA] triplexes of DNG/PNA T-10, with DNA dA(10), are more stable than DNA DNA triplexes [(T-10)(2). dA(10)]. The binding of DNG/PNA chimera with guanidinium linkages on both ends, with single strand length-matched complementary DNA under thermal melt conditions and with longer double strand DNA under isothermal conditions is sequence specific. The association process of DNG/PNA chimera with single strand DNA and strand invasion of longer ds-DNA is faster than the association of PNA, with the same DNA targets, as evident by thermal hysteresis and gel retardation under isothermal conditions. The sequence specific and faster strand invasion of DNG/PNA may extend the potential utility of PNA in diagnostics, biomolecular probes, and antisense/antigene therapeutics.