The binding of analogues of coralyne and related heterocyclics to DNA triplexes

Abstract

Coralyne has been shown previously to bind well to both T.A.T- and C.G.C(+)-containing triplexes. Derivatives of coralyne were prepared and their binding to poly(dT).poly(dA).poly(dT) and poly[d(TC)].poly[d(GA)].poly[d(C+T)] was assessed from thermal denaturation profiles. A tetraethoxy derivative showed only weak binding to both types of triplex. Analogues with extended 8-alkyl chains showed good binding to poly(dT).poly(dA).poly(dT), but the preference for triplex poly[d(TC)].poly[(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 triplex. It is hypothesized that the position of the protonated nitrogen ring is important for binding to poly[d(TC)].poly[d(GA)].poly[d(C+T)]. A series of other chromophores was studied and only those with a positive charge bound to triplexes. 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, most of them did not bind well to the triplex 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 triplex poly(dT).poly(dA).poly(dT) compared with the duplex is a common feature of intercalating drugs. On the other hand, specificity for protonated triplexes may be very difficult to achieve.