The subject of four-stranded nucleic acid structures is reviewed. Studies on gels formed by guanosine and its analogues have provided appropriate models for the structures of poly(I) and poly(G). T...

Four-Stranded Nucleic Acid Structures 25 Years Later: From Guanosine Gels to Telomer DNA

The disclosure describes new compositions of matter that are analogs of DNA and RNA containing heterocyclic bases that can form base pairs that fit the Watson-Crick geometry in that they involve a monocyclic six membered ring pairing with a fused bicyclic heterocyclic ring system composed of a five member ring fused with a six membered ring, with the orientation of the heterocycles with respect to each other and with respect to the backbone chain analogous to that found in DNA and RNA, but where these base pairs are joined by a pattern of hydrogen bonds different from that found in the AT and GC base pairs (a "non-standard base pair").

Oligonucleotides with non-standard bases and methods for preparing same

Why Pentose- and Not Hexose-Nucleic Acids? Purine-Purine Pairing in homo-DNA: Guanine,Isoguanine, 2,6-Diaminopurine, and Xanthine This paper concludes the series of reports in this journal [1–4] on the chemistry of homo-DNA, the constitutionally simplifie dmodel system of hexopyranosyl-(6′ → 4′)-oligonucleotide systems stidued in our laboratory as potentially natural-nucleic-acid alternatives in the context of a chemical aetiology of nucleic-acid structure. The report describes the synthesis and pairing properties of homo-DNA oligonucleotides which contain as nucleobases exclusively purines, and gives, together with part III of the series [3], a survey of what we know today about purine-purine pairingin homo-DNA. In addition, the paper discusses those aspects of the chemistry of homo-DNA which, we think, influence the way how some of the structural features of DNA (and RNA) are to be interpreted on a qualitative level. Purine-purine pairing occurs in the homo-DNA domain in great variety. Most prominent is a novel tridentate Watson-Crick pair between guanine and isoguanine, as well as one between 2,6-diaminopurine and xanthinone, both giving rise to very stable duplexes containing the all-purine strands in antiparallel orientation. For the guanine-isoguanine pair, constitutional assignment is based on temperature-dependent UV and CD spectroscopy of various guanine- and isoguanine-containg duplexes in comparison with duplexes known to be paired in the reverse guanine is replaced by 7-carbauguanine. Isoguanine and 2,6-diaminopurine also have the capability of self-pariring in the reverse-Hoogsteen mode, as previously observed for adenine and guanine [3]. In this type of pairing, the interchangeably. Fig. 36 provides an overall survey of the relative strength of pairing in all possible purine-purine combinations. Watson-Crick pairing of isoguanine with guanine demands the former to participate in its 3H-tautomeric form; hitherto this specific tautomer had not been considered in the pairing chemistry of isoguanine. Whereas (cumulative) purine-purine pairing in DNA (reverse-Hoogsten or Hoogsteen) seems to occur in triplexes and tetrapalexes only, its occurrence in duplexes in a characteristic feature of homo-DNA chemistry. The occurrence of purine-purine Watson-Crick base pairs is probably a consequence of homo-DNA's quasi-linear ladder structure [1][4]. In a double helix, the distance between the two sugar C-atoms, on which a base pair is anchored, is expected to be constrained by the dimensions of the helix; in a linear duplex, however, there would be no restrictions with regard to base-pair length. Homo-DNA's ladder-like model also allows one to recognize one of the reasons why nucleic-acid duplexes prefer to pair in antiparallel, rather than parallel strand orientation: in homo-DNA duplexes, (averaged) backbone and base pair axes are strongly inclined toward one another [4]; the stronger this inclination, the higher the preference for antiparallel strand orientation is expected to be (Fig. 16). In retrospect, homo-DNA turns out to be one of the first artificial oligonucleotide systems (cf. Footnote 65) to demonstrate in a comprehensive way that informational base pairing involving purines and pyrimidines is not a capability unique to ribofuranosyl systems. Stability and helical shape of pairing complexes are not necessary conditions of one another; it is the potential for extensive conformational cooperativity of hte backbone structure with respect to the constellational demands of base pairing and base stacking that determines whether or nor a given type of base-carrying backbone structure is an informational pairing system. From the viewpoint of the chemical aetiology of nucleic-acid structure, which inspired our investigations on hexopyranosyl-(6′ → 4′)-oligonucleotide systems in the first place, the work on homo-DNA is only an extensive model study, because homo-DNA is not to be considered a potential natural-nucleic-acid altenratie. In retrospect, it seems fortunate that the model study was carried out, because without it we could hardly have comprehended the pairing behavior of the proper nucleic-acid alternatives which we have studied later and which will be discussed in Part VI of this series. The English footnotes to Fig. 1–49 provide an extension of this summary.

Warum Pentose‐ und nicht Hexose‐Nucleinsäuren??. Teil V. (Purin‐Purin)‐Basenpaarung in der homo‐DNS‐Reihe: Guanin, Isoguanin, 2,6‐Diaminopurin und Xanthin

[*] Prof. J. T. Davis, M. Cai, Dr. A. L. Marlow, Dr. J. C. FettingerDepartment of Chemistry and BiochemistryUniversity of MarylandCollege Park, MD 20742 (USA)Fax: ( ⁄1)301-314-9121E-mail: jd140@umail.umd.eduProf. D. FabrisDepartment of Chemistry and BiochemistryUniversity of MarylandBaltimore County, Baltimore, MD 21228 (USA)T. J. Haverlock, Dr. B. A. MoyerChemical and Analytical Sciences DivisionOak Ridge National Laboratory, P.O. Box 2008Oak Ridge, TN 37831-6119 (USA)[**] This research was supported by the Separations and AnalysisProgram, Division of Chemical Sciences, Office of Basic EnergySciences, U.S. Department of Energy. J.T.D. thanks the DreyfusFoundation for a Teacher-Scholar Award. We thank Drs. BryanEichhorn, Steve Rokita, and Lyle Isaacs for advice.Supporting information for this article is available on the WWWunderhttp://www.wiley-vch.de/home/angewandte/ or from the author.

Binding Cesium Ions with Nucleosides: Templated Self‐Assembly of Isoguanosine Pentamers

The mononucleoside, 5‘-(tert-butyldimethylsilyl)-2‘,3‘-O-isopropylidene isoguanosine (isoG) 2, has a strong affinity for alkali metal cations. Previously, it was shown that isoG 2 self-assembles via hydrogen bonds to give a stable tetramer, (isoG)4 4, in organic solvents (Davis et al. J. Org. Chem. 1995, 60, 4167−4176). The isoG tetramer 4 can then coordinate metal cations. In this present study, vapor phase osmometry and further 1H NMR experiments confirmed that isoG 2 self-assembles via complementary hydrogen bonds to form tetramer 4. Molecular models obtained from molecular dynamics and MM2 energy minimization indicate that the isoG tetramer 4 is bowl-shaped, with four C2 oxygens located on the tetramer's convex surface. It is likely that these four oxygens on the tetramer's convex face coordinate cations. Potassium picrate was used to determine the stoichiometry of the isoG-K+ complex and its K+ binding affinity. Both 1H NMR and UV−vis spectroscopic analysis demonstrated that isoG 2 forms an octamer, ...

Self-Assembled Ionophores. An Isoguanosine-K+ Octamer

Isoguanosine-5'-pyrosphosphate, in the presence of an oligonucleotide primer, was polymerized by Escherichia coli polynucleotide phosphorylase under conditions analogous to those required for polymerization of 5'-GMP. The resulting poly(isoguanylic acid), poly(isoG), was a multistranded helix with a stability considerably higher than that of poly(G), and fully resistant to various nucleolytic enzymes. The polymer exhibited a two-step temperature transition profile in moderately alkaline propylene glycol. Alkaline titration in aqueous medium, by ultraviolet and circular dichroism spectroscopy, showed two clearly defined transitions, the second of which was fully cooperative. The accompanying changes in sedimentation constants were consistent with a structure for poly(isoG) of a fourstranded helix, like neutral poly(G). In acid medium, spectral and potentiometric titrations demonstrated the existence of more than one transition in the pH range 6-12, with accompanying protonation of the isoguanosine residues. In neutral medium the polymer formed no complexes with other potentially complementary homopolymers. In acid medium, on the other hand, the protonated form of poly(isoG) did form a triple-stranded complex with poly(I), viz. 2poly(I) . poly(isoG)+. Possible structures are formulated for the neural and protonated forms of poly(isoG) which account for the two-step thermal transition in alkaline propylene glycol and on alkaline titration in aqueous medium. The nature of the protonated form, and its complex with poly(I) is also discussed.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1976.tb10404.x

Magdalena Fikus

Papers

Preparation and properties of an analogue of poly(A) and poly(G): poly(isoguanylic acid).