The binding of polyamines, including spermidine (1) and spermine (2), to poly[d(G-C).d(G-C)] was probed using spectroscopic studies of anthracene-9-carbonyl-N1-spermine (3); data from normal absorption, linear dichroism (LD), and circular dichroism (CD) are reported. Ligand LD and CD for transitions located in the DNA region of the spectrum were used. The data show that 3 binds to DNA in a manner characteristic of both its amine and polycyclic aromatic parts. With poly[(dG-dC).(dG-dC)], binding modes are occupied sequentially and different modes correspond to different structural perturbations of the DNA. The most stable binding mode for 3 with poly[d(G-C).d(G-C)] has a site size of 6 +/- 1 bases, and an equilibrium binding constant of (2.2 +/- 1.1) x 10(7) M-1 with the anthracene moiety intercalated. It dominates the spectra from mixing ratios of approximately 133:1 until 6:1 DNA phosphate: 3 is reached. The analogous data for poly[d(A-T).d(A-T)] between mixing ratios 36:1 and 7:1 indicates a site size of 8.3 +/- 1.1 bases and an equilibrium binding constant of (6.6 +/- 3.3) x 10(5) M-1. Thus, 3 binds preferentially to poly[d(G-C).d(G-C)] at these concentrations.
I n recent years, a systematic program of research has led to the development of an ideological surround model of the psychology of religion (Watson, 1993, 1994). This model asserts that all research in the psychology of religion operates within a surround of ideological influences. "Ideology" in this instance refers to a somewhat non-empirical, normative, and sociological system of belief (MacIntyre, 1978, pp. 5-6). Most contemporary psychologists, for example, adopt a naturalistic ideological perspective. Innumerable scientific observations support naturalism, but the ultimate truth of the position currently lies beyond definitive empirical proof, making it somewhat non-empirical. Naturalism, nevertheless, has normative implications in that it differentiates between "good" and "bad" forms of belief. Causal explanations in terms of reductive materialistic processes tend to be "good." Beliefs in supernatural causes like God and Satan are "bad." At a sociological level, even an implicit commitment to this ideology unites a researcher with a large community of like-minded scholars. A Christian research program would, of course, be every bit as sociological, normative, and somewhat non-empirical as a naturalistic or any other approach to the psychology of religion. Within a pluralistic cultural environment, no wholly objective,
We have used hydroxy-radical and deoxyribonuclease-I footprinting to probe the interaction of mithramycin with DNA fragments containing the sequences (AT),,X(AT),, (X = CCCG, CCGC or CGGC) and A,,GCCCT,,. As expected the drug produces clear footprints located around the central four GC base pairs. The exact position of the footprint is different for the four sequences; the footprint with CCCG is displaced by two base pairs in the 5' direction relative to GCCC. These variations are explained by suggesting that mithramycin avoids the dinucleotide CG and binds better to GG/CC than GC. Although there is little change in deoxyribonuclease-I cleavage of the surrounding blocks of (AT),, cleavage by deoxyribonuclease I1 is markedly enhanced and certain thymines on the 5' side of the ligand-binding site become hyperreactive to hydroxy-radical attack. Adjacent regions of A, ' T, show enhanced rates of deoxyribonuclease-I cleavage in the presence of the antibiotic.Mithramycin, and the related aureolic acid antibiotics chromomycin and olivomycin, have long been known to bind to GC-rich regions of DNA [l-21, in a reaction which requires stoichiometric quantities of divalent metal ions, especially magnesium [3]. These compounds do not interact with AT-rich sequences and appear to require the presence of a purine 2-amino group [4, 51. Various footprinting studies, using deoxyribonuclease I (DNase I) [6, 71, MPE-Fe(1I) [S] and hydroxy radicals [9] have confirmed the GC selectivity and suggest that the ligand binding requires at least two contiguous guanines ; the best dinucleotide binding site is thought to be GpG. However two adjacent GC residues do not necessarily constitute a good binding site as indicated by NMR studies which failed to detect binding to a sequence containing a single CpG site [lo]. In addition the antibiotics do not produce footprints at all GC-rich sites, even at some which contain three contiguous GC base pairs [9].The molecular details of their interaction with DNA have been revealed by several high-resolution NMR studies [ 10 -151. These have shown that mithramycin and chromomycin bind as dimers within the DNA minor groove coordinating a single magnesium ion. Selective binding to GC sequences is achieved by the formation of hydrogen bonds between the C8 phenolic group of the antibiotic and the guanine N3 and 2-NH2 groups. The first complexes contained the tetranucleotide GGCC, which bound a single chromomycin dimer [11]. Subsequent studies have shown specific binding to isolated GC and GG but not CG sites. In each case the drug binds as a dimer with the chromomycinone ring positioned over the guanines with the sugar residues extending in the 3' direction. When two GG half-sites are separated by two AT base
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