Unique Cooperative Binding Interaction Observed between a Minor Groove Binding Pt Antitumor Agent and Hoeschst Dye 33258

Abstract

The trinuclear compound [{Pt(NH3)3}2mu-{trans-Pt(NH3)2(H2N(CH2)6NH2)}2(6+) (0,0,0/t,t,t) binds to DNA only through noncovalent hydrogen bonding and electrostatic interactions. The presence of this 6+ cation allows discrimination of binding modes for common DNA ligands: binding of minor-groove agents such as Hoechst 33258 is cooperative, and dye-DNA interaction is enhanced whereas intercalation as exemplified by ethidium bromide is competitively inhibited.

Polyamines: fundamental characters in chemistry and biology

“…In particular, a group of cisplatin-like compounds containing polyamine bridging ligands (putrescine, spermidine or spermine) have proven to display novel antitumour properties (Qu et al 2000;Marques et al 2002a, b;Teixeira et al 2004;Harris et al 2006;Komeda et al 2006;Fiuza et al 2006) due to the formation of a new type of DNA adducts, through long-distance intra-and interstrand cross-links or by noncovalent interactions, not available to the conventional alkylating agents (e.g. triplatinum BBR3464) (Qu et al 2000;Pratesi et al 1999) and Triplatinum NC, (Komeda et al 2006;Harris et al 2005).…”

2D NMR Spectroscopic Evidence for Unprecedented Interactions of cis‐[Rh2(dap)(μ‐O2CCH3)2(η1‐O2CCH3)(CH3OH)](O2CCH3) with a DNA Oligonucleotide: Combination of Intercalative and Coordinative Binding

“…There are, however, a few cases of inorganic or organometallic antitumor agents that incorporate more than one metal unit, for example, by introducing a hydrocarbon chain or polypeptide unit to form a multifunctional complex with improved binding affinity to DNA. Examples of systems under study are polynuclear platinum complexes, [6][7][8][9][10][11][12] compounds with one or more intercalative binding units, [3,13,14] and metal complexes with bifunctional coordinative and intercalative binding units. [8][9][10][11][12][15][16][17][18][19][20] There are also reports of intercalative and coordinatively bound organometallic ruthenium(II) anticancer complexes that possess both an intercalating arene group and a labile chloride ligand.…”

“…Examples of systems under study are polynuclear platinum complexes, [6][7][8][9][10][11][12] compounds with one or more intercalative binding units, [3,13,14] and metal complexes with bifunctional coordinative and intercalative binding units. [8][9][10][11][12][15][16][17][18][19][20] There are also reports of intercalative and coordinatively bound organometallic ruthenium(II) anticancer complexes that possess both an intercalating arene group and a labile chloride ligand. [21][22][23] Among the many metal complexes that are known to exhibit antitumor activity are dirhodium compounds that establish coordinative interactions with DNA [24,25] with a preference for the N7 sites of adenine and guanine.…”

Biological Consequences of Trinuclear Platinum Complexes: Comparison of [{trans-PtCl(NH3)2}2μ-(trans-Pt(NH3)2(H2N(CH2)6-NH2)2)]4+ (BBR 3464) with Its Noncovalent Congeners

“…They still associate with DNA with high affinity, however, producing B-to-A and B-to-Z transitions in susceptible sequences at concentrations lower than those required by cobalt hexammine (Qu et al, 2004). I and II displace ethidium bromide from DNA and increase the binding affinity for Hoechst dye in an adenine/thymine-rich 12-mer (Harris et al, 2005b). These noncovalent compounds have also been shown to associate with the adenine/thymine regions of the DNA minor groove (Harris et al, 2005a).…”