Conformations of cyclic 3',5'-nucleotides. Effect of the base on the synanti conformer distribution

The furanose and the phosphate rings of cyclic 3′,5′-nucleotides are locked in the ₄T³ and chair conformations respectively. The only variable which shows major conformational flexibility in these molecules is the rotation about the glycosyl bond which describes the orientation of the base relative to the sugar-phosphate bicyclic system. The glycosyl torsion angle has been analyzed for cyclic nucleotides with different purine and pyrimidine bases by use of conformational energy calculations. The results indicate that all the pyrimidine bases, U, T and C show a very strong energetic preference for the anti range of conformations. The calculations predict that among cyclic 3′,5′-purine nucleotides cyclic GMP and cyclic IMP favor the syn conformation to the anti by 95:5 and 70:30 respectively, while cyclic AMP shows a preference for the anti conformation to syn by 70:30. Thus the purines show a greater probability for the syn conformation than the pyrimidines in cyclic 3′,5′-nucleotides.     

Syn-anti effects on the spatial configuration of polynucleotide chains

Semiempirical energy calculations have beeb performed on model nucleic acid systems to assess the preferred conformation of the rotation χ about the glycosidic linkage and also the effect of this rotation on the spatial configuration of the sugar-phosphate chain backbone. The rotation angle ?? about bond C_5′–C_4′ in purine polyribonucleotides and 5′-monoribonucleotides is found to depend on whether the conformational range of χ is syn or anti. The preferred conformation of χ in these molecules is also found to depend upon the nature of the attached base. The orientation of χ in poly rA chains is predicted to be predominantly anti, whereas in poly rG the syn conformer is expected to occur in significant proportions. The syn conformer is preferred almost exclusively in certain unusual purine polynucleotides, such as poly 8Br-rA. It is noted that the preferred conformation of x in polynucleotides is not necessarily the same as that calculated for 5′-mononucleotides and nucleosides. On the basis of these calculations, the influence of the orientation and nature of a purine base on the spatial configuration of a polynucleotide chain as a whole has been examined. The random coil dimensions of a syn polynucleotide chain are found to be larger than those of an anti chain as a consequence of the effect of a syn base on the local conformation of the chain skeleton. Finally, it is found that the occurrence of a syn base in an ordered polynucleotide chain may prevent the formation of normal stacking with the preceding base.     

The occurrence of the syn-C3′ endo conformation and the distorted backbone conformations for C4′-C5′ and P-O5′ in oligo and polynucleotides

Abstract

The nucleoside constituents of nucleic acids prefer the anti conformation (1). When the sugar pucker is taken into account the nucleosides prefer the C2′endo-anti conformation. Of the nearly 300 nucleosides known, about 250 are in the anti conformation and 50 are in the syn-conformation, i.e., anti to syn conformation is 5:1. The nucleotide building blocks of nucleic acids show the same trend as nucleosides. Both the deoxy-guanosine and ribo- guanosine residues in nucleosides and nucleotides prefer the syn-C2′endo conformation with an intra-molecular hydrogen bond (for nucleosides) between the O5′- H and the N3 of the base and, a few syn-C3′endo conformations are also observed. Evidence is presented for the occurrence of the C3′endo-syn conformation for guanines in mis-paired double helical right-handed structures with the distorted sugar phosphate C4′-C5′ and P-O5′ bonds respectively, from g+ (gg) and g- to trans. Evidence is also provided for guanosine nucleotides in left-handed double-helical (Z-DNA) oligo and polynucleotides which has the same syn-C3′endo conformation and the distorted backbone sugar-phosphate bonds (C4′-C5′ and P- O5′) as in the earlier right-handed case.     

The electronic structure of and conformational energy barrier to rotation a round the C-N glycosidic linkage in adenosine-3',5'-cyclicmonophosphate (cyclic AMP) and its phosphonate analog

Extended Hückel molecular orbital calculations are reported on cyclic AMP and its phosphonate analog. A parallel Lennard-Jones potential and molecular orbital study on the barrier to rotation of the adenine base around the sugar phosphate moiety indicates a rather low barrier for both molecules studied (6.6 kcal/mole and less than 6 kcal/mole for the cyclic phosphate and cyclic phosphonate, respectively) with most favorable syn and anti forms possessing similar energies. According to the calculations this low barrier may be the most distinguishable property when compared to the molecule's precursor ATP and enzymically derived product 5′-AMP.     

Conformational studies on pyrimidine 5'-monophosphates and 3',5'-diphosphates. Effect of the phosphate groups on the backbone conformation of polynucleotides

In continuation of our studies on the effect of the base and the phosphate groups on the glycosyl and the sugar-phosphate backbone conformation, we have carried out semi-empirical potential energy calculations on the common 5′- and 3′5′-ribopyrimidine mono- and diphosphates by considering simultaneous rotations about the glycosyl (χ) and the C(4′)–C(5′) (ψ) bonds. This calculation provides an assessment of the nature and orientation of the base on the sugar–phosphate backbone conformation of nucleotides and polynucleotides. It is found that the attractive inetractions between the 5′-phosphate group and the base mutually stabilize the antiand the gauche-gauche (gg) conformations about χ and ψ, respectively, in 5′-ribopyrimidine nucleotides. The introduction of the 3′-phosphate group as in 3′,5′-ribopyrimidine diphosphates, still leaves the anti-gg as the most favored conformation with the important difference that the probability of occurrence of the anti, gauche-trans (gt) is how substantially increased. This is dependent to a large extent on the sugar conformation and to a lesser extent on the base. Uracil and thymine show a greater probability for the anti-gt than cytosine. The syn conformation is considerably less likely and its occurrence is also dependent on the base type, cytosine showing a lesser tendency than uracil and thymine. For the syn base, the most favourec conformation for ψ is gt, since gg is sterically disallowed and tg is destabilized by electrostatic repulsive interactions between the 3′ and 5′-phosphate groups. Thus, there is a striking correlation between the glycoysl and the backbone C(4′)–C(5′) bond conformations. The rest of the bonds of the backbone are considerable less dependent on the glycosyl conformation. These studies reveal that in poly-ribopyrimidine nucletides the majority of the nucleotide residues are expected to occur in the anti-gg conformation.     

Far-infrared absorption of nucleotides and poly(I)·poly(C) RNA

We have measured the ir absorption of 5′CMP, 5′IMP, and poly(I)·poly(C) from ～25 to ～500 cm^?1. From a comparison of the data with the previously measured absorption of the corresponding nucleosides and bases we can identify several “lines” associated with the deformation of the ribose ring. Out-of-plane deformation of the bases contributes strongly to vibrations near 200 cm^?1. The same ribose vibrations observed in the nucleotides are found in poly(I)·poly(C). They sharpen with increasing water absorption. A study of the spectra of poly(I)·poly(C) as a function of the adsorbed water indicates that water does not contribute in a purely additive fashion to the polynucleotide spectrum but depends on the conformation of the helix. However, the only spectral feature that shifts drastically with conformation is near 45 cm^?1. Measurements at cryogenic temperatures indicate some sharpening of the spectrum of poly(I)·poly(C). Instead, no sharpening is observed in the spectrum of the nucleotides. Shear degradation of poly(I)·poly(C) produces significant spectral changes in the 200-cm^?1 region and sharpening of the features assigned to the low-frequency ribose-ring vibrations.     

Pyrimidine nucleoside analogues as inducers of pyrimidine nucleoside catabolizing enzymes in salmonella typhimurium

Various structural analogues of cytosine and uracil nucleosides were tested as potential inducers of the nucleoside catabolizing (cyt) enzymes in Salmonella typhimurium. Some analogues, e.g. 5′-O-alkyl cytidines and uridines, resistant to catabolic enzymes, were as effective as the natural inducers cytidine and uridine; but etherification of one of the cis 2′ or 3′hydroxyls fully abolished activity, pointing to a requirement of an intact ribose cis-glycol system for activity. A uridine analogue in the syn conformation, 6-methyluridine, a good substrate for uridine phosphorylase, was inactive as an inducer. The behaviour of various other analogues, in relation to their structure, conformation and substrate properties, indicated the absence of any correlation between inducing activity and substrate susceptibility. The overall findings are consistent with conclusions derived from genetic experiments. The active analogues apparently act via similar pathways, and probably affect the same regulatory mechanism(s) as the natural inducers.     

Crystallographic studies of drug-nucleic acid interactions: Proflavine intercalation between the non-complementary base-pairs of cytidilyl-3′,5′-adenosine

In order to get insights into the binding of dyes and mutagens with denatured and single-stranded nucleic acids and the possible implications in frameshift mutagenesis, a 1:1 complex between the non-self-complementary dinucleoside monophosphate cytidilyl-3′,5′-adenosine (CpA) and proflavine was crystallized. The crystals belong to the tetragonal space group P4₂2₁2 with cell constants $\text{a = b = 19.38(1)}\text{A}\text{?}\text{and}\text{c = 27.10(1)}\text{A}\text{?}$. The asymmetric unit contains one CpA, one proflavine and nine water molecules by weight. The structure was determined using Patterson and direct methods and refined to an R-value of 11% using 2454 diffractometer intensities.The non-self-complementary dinucleoside monophosphate CpA forms a selfpaired parallel chain dimer with a proflavine molecule intercalated between the protonated cytosine-cytosine (C · C) pair and the neutral adenine-adenine (A · A) pair. The dimer complex exhibits a right-handed helical twist and an irregular girth. The neutral A · A pair is doubly hydrogen-bonded through the N(6) and N(7) sites (C(1′)C(1′) distance: 10.97(2) Å) and the protonated C · C pair is triply hydrogen-bonded with a proton shared between the N(3) sites (C(1′)C(1′) distance: 9.59(2) Å). To accommodate the intercalating dye, the sugars of successive nucleotide residues adopt the two fundamental conformations (5′ end: 3′-endo, 3′ end: 2′-endo), the backbone adopts torsion angle values that fluctuate within their preferred conformational domains: the PO bonds (ω, ω′) adopt the characteristic helical (gauche^?-gauche^?) conformation, the CO bonds (φ, φ′) are both in the trans domain and the C(4′)C(5′) bonds (ψ) are in the gauche⁺ region. The bases of both residues are disposed in the preferred anti domain with the glycosyl torsion angles (χ) correlated to the puckering mode of the sugar so that the cytidine residue is C(3′)-endo, low χ (12 dg), and the adenosine residue is C(2′)-endo, high χ (84 °). The intercalated proflavine stacks more extensively with the C · C pair than the A · A pair. Between 4₂-related CpA proflavine units there is a second proflavine which stacks well with both the A · A and the C · C pairs sandwiching it. Both proflavine molecules are positionally disordered. In each of its two disordered sites, the intercalated proflavine forms hydrogen-bonded interactions with only one sugar-phosphate backbone. A total of 26 water sites has been characterized of which only two are fully occupied. These hydration sites are involved in an intricate network of hydrogen bonds with both the dye and CpA and provide insights on the various modes of interactions between water molecules and between water molecules and nucleic acids.The structure of the proflavine-CpA complex shows that intercalation of planar drugs can occur between non-complementary base-pairs. This result can be relevant for understanding the strong binding of acridine dyes to denatured DNA, single-stranded RNA, and single-stranded polynucleotides. Also, the ability of proflayine to promote self-pairs of adenine and cytosine bases could provide a chemical basis for an alternative mechanism of frameshift mutagenesis.     

The anti/syn conformation of 8-oxo-7,8-dihydro-2′-deoxyguanosine is modulated by Bacillus subtilis PolX active site residues His255 and Asn263. Efficient processing of damaged 3′-ends

8-oxo-7,8-dihydro-2′-deoxyguanosine (8oxodG) is a major lesion resulting from oxidative stress and found in both DNA and dNTP pools. Such a lesion is usually removed from DNA by the Base Excision Repair (BER), a universally conserved DNA repair pathway. 8oxodG usually adopts the favored and promutagenic syn-conformation at the active site of DNA polymerases, allowing the base to hydrogen bonding with adenine during DNA synthesis. Here, we study the structural determinants that affect the glycosidic torsion-angle of 8oxodGTP at the catalytic active site of the family X DNA polymerase from Bacillus subtilis (PolXBs). We show that, unlike most DNA polymerases, PolXBs exhibits a similar efficiency to stabilize the anti and syn conformation of 8oxodGTP at the catalytic site. Kinetic analyses indicate that at least two conserved residues of the nucleotide binding pocket play opposite roles in the anti/syn conformation selectivity, Asn263 and His255 that favor incorporation of 8oxodGMP opposite dA and dC, respectively. In addition, the presence in PolXBs of Mn²⁺-dependent 3′-phosphatase and 3′-phosphodiesterase activities is also shown. Those activities rely on the catalytic center of the C-terminal Polymerase and Histidinol Phosphatase (PHP) domain of PolXBs and, together with its 3′-5′ exonuclease activity allows the enzyme to resume gap-filling after processing of damaged 3′ termini.     

Barrier potentials,molecular structure,force filed calculations and quantum chemical studies of some bipyridine di-carboxylic acids using the experimental and theoretical using (DFT,IVP) approach

ABSTRACT

FT-IR and FT-Raman spectra of 2,2′-bipyridine-3,3′-dicarboxylic acid (B3DA), 2,2′-bipyridine-4,4′-dicarboxylic acid (B4DA) and 2,2′-bipyridine-5,5′-dicarboxylic acid (B5DA) were recorded and analysed. The quantum chemical calculations of the title compounds begin with barrier potentials at different rotation angles around the C–C′ and C–Cα bonds in order to arrive conformation of lowest energy using DFT employing B3LYP functional with 6-311++G(d,p) basis set. This confirmation was further optimised to get the global minimum geometry. The vibrational frequencies along with IR, Raman intensities were computed, the rms error between observed and calculated frequencies were 11.2 cm^?1, 10.2 cm^?1 and 12.2 cm^?1 for B3DA, B4DA, and B5DA. An 87-element modified valence force field is derived by solving the inverse vibrational problem using Wilson’s GF matrix method. This force field is refined using 163 observed fundamentals employing in overlay least-squares technique. The average error between computed and experimental frequencies was found as 12.85 cm^?1 using potential energy distribution (PED) and eigenvectors. By using the gauge-independent atomic orbital (GIAO) method calculate the ¹H and ¹³C NMR chemical shifts of the molecules and compared with experimental results. The first-order hyperpolarisability, HOMO and LUMO energies, molecular electrostatic potential (MESP) and natural orbital analysis (NBO) of titled compounds were evaluated using DFT.     

Conformational characteristics of polypeptides containing isolated L-proline residues with cis peptide bonds

The conformational characteristics of the peptide sequence X-l-Pro, where X  Gly or l-Ala and the peptide bond joining X and l-Pro is cis, are evaluated. Semi-empirical potential functions are used to estimate the contributions to the conformational energy made by the non-bonded van der Waals' and electrostatic interactions and the intrinsic torsional potentials about the NC^a and C^aC′ bonds. Rotations φ₁ and ψ₁ about the NC^a and C^aC′ bonds in residue X and rotation ψ₂ about the C^aC′ bond in l-Pro are permitted, while the angle of rotation φ₂ about the NC^a bond in l-Pro is fixed at 120 ° by the pyrrolidine ring. The presence of the cis peptide bond connecting X and l-Pro renders the backbone rotations φ₁, ψ₁ in X dependent upon the rotation ψ₂ about the C^aC′ bond in l-Pro. (Interdependence of rotations in neighboring residues joined by a cis peptide bond was previously observed in l-alanine oligomers.) The number of energetically allowed conformations for the Gly and l-Ala residues preceding a cis peptide bond l-Pro residue are found to be substantially reduced from those permitted when the peptide bond is trans or when l-Pro is replaced by an amino acid residue. On the other hand, ψ₂ = 100 to 160 ° (cis′) and 300 to 0 ° (trans′) are found to be the lowest energy conformations of the l-Pro residue irrespective of the cis or trans conformation of the X-l-Pro peptide bond.     

A new anti conformation for N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG) allows Watson-Crick pairing in the Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4)

Primer extension studies have shown that the Y-family DNA polymerase IV (Dpo4) from Sulfolobus solfataricus P2 can preferentially insert C opposite N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG) [F. Boudsocq, S. Iwai, F. Hanaoka and R. Woodgate (2001) Nucleic Acids Res., 29, 4607–4616]. Our goal is to elucidate on a structural level how AAF-dG can be harbored in the Dpo4 active site opposite an incoming dCTP, using molecular modeling and molecular dynamics simulations, since AAF-dG prefers the syn glycosidic torsion. Both anti and syn conformations of the templating AAF-dG in a Dpo4 ternary complex were investigated. All four dNTPs were studied. We found that an anti glycosidic torsion with C1′-exo deoxyribose conformation allows AAF-dG to be Watson–Crick hydrogen-bonded with dCTP with modest polymerase perturbation, but other nucleotides are more distorting. The AAF is situated in the Dpo4 major groove open pocket with fluorenyl rings 3′- and acetyl 5′-directed along the modified strand, irrespective of dNTP. With AAF-dG syn, the fluorenyl rings are in the small minor groove pocket and the active site region is highly distorted. The anti-AAF-dG conformation with C1′-exo sugar pucker can explain the preferential incorporation of dC by Dpo4. Possible relevance of our new major groove structure for AAF-dG to other polymerases, lesion repair and solution conformations are discussed.     

On the conformational dependence of the proton chemical shifts in nucleosides and nucleotides III. Proton chemical shifts of 5′-nucleotides as a function of different conformational parameters

The variation of the chemical shift of the protons of 5′-UMP and 5′-AMP is calculated as a function of χ_CN, ψ and ? torsion angles. The shift of H8 of 5′-AMP and H6 of 5′-UMP is found to be very sensitive to the value of χ_CN. For the anti conformations the shift of these protons is more sensitive to the value of the rotation about CS′-05′ than about C4′-CS′. For the protons of the ribose the calculations show that for the C2′-endo pucker H3′ and H2′ undergo the largest chemical shift variations when ? and ψ vary. The calculated variations are considered in relation with the role of the conformation of the nucleotides in the chemical shift variation between mono and polynucleotides and between the different helical structures of polynucleotides.     

Etude cristallographique des β-d-glucopyranosyl- et β-d-mannopyranosyl-benzènes acétylés,analogues de nucléosides pyrimidiques

The structures of the two title C-glycopyranosylarene nucleosides have been determined by X-ray diffraction. The aim of this work was to relate the conformation around the extracyclic C-1C-7 bond to steric hindrance between the pyranose and benzene rings. The torsion angles observed in the two compounds (O-5C-1C-7C-8: +61,7° for 1, ?13,4° for 2) signify of a C-2 configurational modification. Moreover, the interaction between O-5 and an o-phenyl hydrogen could explain the particular conformation of the aryl substituent in 2.     

Conformation of adenosine 3′,5′-monophosphate in solution as studied by the NMR-desert method II. Self-association and temperature-dependent glycosidic isomerization at pH 7

A study has been made of the association and the temperature-dependent conformation of adenosine 3′,5′-monophosphate (cyclic AMP) in a neutral aqueous (²H₂O) solution by means of proton magnetic resonance chemical shift and relaxation. The concentration and temperature-dependent chemical shifts of H(1′), H(2), and H(8), have enabled us to estimate the self-association constant, K_a = 1.1 ± 0.3 M^?1 at 25°C and thermodynamic parameters ΔH = ?5.8 ± 1.5 kcal/mol and ΔS (25°C) = ?19.0 ± 3 cal/mol per degree.The NMR-DESERT (Deuterium Substitution Effect on Relaxation Times) method has been utilized for the determination of the syn-anti conformational equilibrium in the monomeric state and for the determination of the mutual orientation of the two adenine rings in the dimeric state of cyclic AMP. The molecules were found to coexist with nearly equimolarity of syn-anti conformers and thermal activation of the molecules perturbs the syn-anti conformational equilibrium to comprise the syn form in preference at higher temperature. The glycosidic isomerization (from anti to syn) was found to be characterized both by a positive enthalpy change and by a positive entropy change. The cyclic AMP molecules prefer to take a ‘trans-stacking’ conformation in the dimeric state where the two molecules are arranged in such a way that the H(2) of one molecule is close to the H(8) of the other.     

THE SYNTHESIS OF ANTI-FIXED 3-METHYL-3- DEAZA-2′-DEOXYADENOSINE AND OTHER 3H-IMIDAZO[4,5-c]PYRIDINE ANALOGS

ABSTRACT

Rotation of a heterocyclic base around a glycosidic bond allows the formation of syn and anti conformations in nucleosides. The syn conformation has been observed primarily in purine-purine mismatches in DNA duplexes. Such mismatches give rise to false positive oligonucleotide hybridization in DNA-based diagnostics. Here we describe the synthesis of an analog of 2′-deoxyadenosine that retains its Watson-Crick functional groups, but cannot form the syn conformation. In this analog, the N3 atom of 2′-deoxyadenosine is replaced by a C-CH₃ group to give 7-methyl-1-β-D-deoxyribofuranosyl-1H-imidazo[4,5-c]pyridin-4-ylamine or 3-methyl-3-deaza-2′-deoxyadenosine (3mddA). This modification sterically prevents the syn conformation and 3mddA becomes an anti-fixed nucleoside analog of 2′-deoxyadenosine. The synthesis and conformational analysis of 3mddA and several analogs with an 3H-imidazo[4,5-c]pyridine skeleton are described, as well as their potential applications.     

A molecular orbital study of the conformation of formycin

Semiempirical quantum mechanical calculations, using the iterative extended Huckel theory, are carried out for the evaluation of conformational energies, dipole moment and net atomic charges as a function of the rotation about the glycosidic bond. Torsion about the C(4′)-C(5′) bond has also been considered. The energy diagrams for either the gg or gt rotamers of formycin predict that neither the first or the second energy minimum fall in the classical anti or syn regions. The predicted energy difference between the two most preferred conformations is rather large (3 kcal/mole). In contrast adenosine is predicted to favor the anti conformation by less than 1 kcal/mole. Barriers to internal counter-clockwise rotation about the glycosidic bond are higher for adenosine.     

f-Element/crown ether complexes. 16. Synthesis,crystallization and crystal structure of [Dy(OH2)8]Cl3·18-crown-6·4H2O

When crystals of [Dy(OH₂)₇(OHMe)] [DyCl(OH₂)₂(18- crown-6)]₂Cl₇·2H₂O [1] are allowed to warm from 5 °C to ambient temperature (22 °C) under the original solvent mixture (1:3 CH₃OH: CH₃CN), they redissolve and the title complex can be isolated by slow evaporation of the resulting solution. The crystal structure of this complex, [Dy(OH₂)₈]Cl₃·18-crown-₆·4H₂O, has been determined. It crystallizes in the monoclinic space group, P2₁/c, with a = 10.395(1), b = 18.684(1), c = 16.259- (3) Å, β= 102.56(1)°, and D_calc = 1.61 g cm⁻³ for Z = 4. A final conventional R value of 0.041 was obtained by least-squares refinement using 3453 independent observed [F_o⩾5σ(F_o)] reflections. The [Dy(OH₂)₈]³⁺ cations and crown ether molecules are hydrogen bonded in a polymeric chain with the crown molecules separating the cations and a total of seven DyOH₂···O(crown ether) hydrogen bonds. The chains are connected by a hydrogen bonding network consisting of the cations, chloride ions, and uncoordinated water molecules. The geometry of the cation is best described as a bicapped trigonal prism with distortions on the reaction pathway toward dodecahedral symmetry. The two capping atoms average 2.41(1) Å from Dy, the remaining DyO distances average 2.38(2) Å. The 18-crown-6 molecule has the D_3d conformation normally observed except for a distortion of one OCCO unit containing the oxygen atom accepting two hydrogen bonds.     

Affect of spleen and snake venom phosphodiesterases on nucleotides containing nucleosides in the syn conformation.

Dinucleotides containing 6-methyldeoxyuridine and inosine have been prepared and subjected to spleen and snake venom phosphodiesterases. Spleen enzyme degrades all nucleotides tested while snake venom causes very little degradation of nucleotides having 6-methyldeoxyuridine in the 3′-terminal position. The clear implication is that snake venom will not recognize nucleoside units in the syn conformation.     

Predicted mode of intercalation of doxorubicin with dinucleotide dimers

Intermolecular molecular mechanics energy calculations have been carried out for doxorubicin interacting with two dinucleotide dimer sequences. The preferred mode of intercalation is in the minor groove with the anthraquinone ring of the drug nearly perpendicular to the base pairs for the (CpG) sequence having alternate C3′ endo-C2′ endo sugar ring puckering. The preferred intercalation conformation of the drug is nearly identical to the N-bromacetyldaunomycin crystal structure. This prediction is qualitatively consistent with the recently reported crystal structure of a d(CpGpCpGpCpG) dimer-daunomycin complex. For the other dinucleotide sequence, (TpC-ApG), minor groove intercalation is also preferred, but the drug conformation can be changed.