THE BINDING OF ANALOGS OF CORALYNE AND RELATED HETEROCYCLICS TO DNA TRIPLEXES

Coralyne has been shown previously to bind well to both T . A . T- and C . G . C+-containing triplexes. Derivatives of coralyne were prepare d and their binding to poly(dT). poly(dA). poly(dT) and poly[d(TC)]. p oly[d(GA)]. poly[d(C+T)] was assessed from thermal denaturation profil es. A tetraethoxy derivative showed only weak binding to both types of tripler. Analogues with extended 8-alkyl chains showed good binding t o poly(dT). poly(dA). poly(dT), but the preference for tripler poly[d( TC)]. poly[d(GA)]. poly[d(C+T)] was decreased compared with the duplex . Sanguinarine, a related alkaloid, bound well to poly(dT). poly(dA). poly(dT) but only weakly to the protonated tripler. It is hypothesized that the position of the protonated nitrogen ring is important for bi nding to poly[d(TC)]. poly[d(GA)]. poly[d(C+T)]. A series of other chr omophores was studied and only those with a positive charge bound to t riplexes. All of these bound well to poly(dT). poly(dA). poly(dT) but only weakly if at all to the duplex poly(dA). poly(dT). In contrast, m ost of them did not bind well to the tripler poly[d(TC)]. poly[d(GA)]. poly[d(C+T)] and those that did still showed a preference for duplex poly[d(TC)]. poly[d(GA)]. In general, preference for tripler poly(dT). poly(dA). poly(dT) compared with the duplex is a common feature of in tercalating drugs. On the other hand, specificity for protonated tripl exes may be very difficult to achieve.