Spectroscopic studies on the structure of poly(8‐bromoadenylic acid): Effect of glycosidic torsion angle on the conformation and flexibility in polyribonucleotides

Govil, Girjesh; Fisk, Cherie L.; Howard, Frank B.; Miles, H. Todd

doi:10.1002/bip.1981.360200310

Cited by 17 publications

(19 citation statements)

References 85 publications

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“…2B) as well as the H3'(1) (not shown) of the compounds with brominated A(l) residues resonate downfield with respect to the corresponding protons of the other fragments. Similar observations were made for (3'-5')poly(br8A) by Govil et al [29]. According to these authors [29] the lone pair of N3 is oriented towards the C3'-H3' bond in the case of N-type ribose and syn position of the base which results in a downfield shift of H3'.…”

Section: Chrmicul Shiftssupporting

confidence: 78%

“…Similar observations were made for (3'-5')poly(br8A) by Govil et al [29]. According to these authors [29] the lone pair of N3 is oriented towards the C3'-H3' bond in the case of N-type ribose and syn position of the base which results in a downfield shift of H3'. The H2' resonance is influenced in a similar fashion.…”

Section: Chrmicul Shiftssupporting

confidence: 78%

“…2D) and to a lesser extent H3'(3) of pbrsA2'-5'brsA2'-5'br8A, pA2'-5'br8A2'-5'br8A and pA2'-5'A2'-5'br'A are deshielded with respect to the other compounds. According to Govil et al [29], the C2'-H2' bond is oriented towards the lone pair of N3 in the case of an S-type sugar together with a syn position of the base. This leads to a deshielding of the H2' and to a smaller degree of the H3'.…”

Section: Chrmicul Shiftsmentioning

confidence: 99%

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Conformational analysis of brominated pA2′‐5′A2′‐5′A analogs

Hoogen¹,

Hilgersom²,

Brózda³

et al. 1989

European Journal of Biochemistry

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NMR and model-building studies were carried out on pA2'-5'A2'-5'A and analogs in which one or more of the A residues were replaced by 8-bromoadenosine. Chemical shifts, coupling constants and NOE data were used to obtain structural information. The N/S equilibrium constant of the ribose rings as well as the phase angles and puckering amplitudes were determined from the experimental coupling constants with the aid of an improved version of the PSEUROT program. Chemical shifts in combination with NOE data were used to monitor basebase interactions and the orientation of the bases (syn or anti).The combined data suggest that different types of stacking interactions are present in the various compounds. Bromination of the first or second residue in the trimers results in a preference for N-type sugar and syn orientation of the base in these residues. When A(3) is brominated, an S-type sugar conformation together with a syn orientation of the base is favoured at the 2' terminus. Energy-minimized models of the different stacking interactions are presented which fit the present collection of data. The possible correlation between biological activity of these compounds and their conformation is briefly discussed.During the last decade it has become evident that pppA2'-5'A2'-5'A plays an important role in the antiviral action of interferon (reviewed in [l]) and possibly as a regulator of cell growth and/or differentiation [2 -51. This suggests the possibility to exploit the system to develop a novel chemotherapeutic approach to viral diseases. However, such applications are limited by two barriers : (a) pppA2'-5'A2'-5'A has a short biological half-life due to rapid degradation by a 2',5'-phosphodiesterase and (b) due to its highly negative charge, the molecule is unable to penetrate the cell membrane.A possible solution of these problems appears to lie in a search for modifications of the molecule in such a way that the binding to, and the activation of, the (2'-5')oligo(A)-dependent endonucleases (RNase L) remain comparable to the properties of the parent compound. Thus far, several modifications have been synthesized and tested upon binding and activity [6-91. For example, the 6-amino groups [6], the N7 atoms [6,9] and the 3'-OH functions [8] of the various residues were sequentially replaced in order to examine which of them are crucial for binding and/or activation. Another substitution was the replacement of adenosine by 8-bromoadenosine, not only in the case of the 5'-triphosphate parent Correspondence to C .

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Section: Chrmicul Shiftssupporting

confidence: 78%

Section: Chrmicul Shiftssupporting

confidence: 78%

Section: Chrmicul Shiftsmentioning

confidence: 99%

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Conformational analysis of brominated pA2′‐5′A2′‐5′A analogs

Hoogen¹,

Hilgersom²,

Brózda³

et al. 1989

European Journal of Biochemistry

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“…This determination of anti-conformation of the nucleotides 3 and 4 is also supported by H2′ and H2″ chemical shifts, 2.82 and 2.68 for 4 and 2.85 and 2.76 ppm for 3. 21,37 The bond-length between the Zn 2+ ion and phosphate oxygen atoms in most inner sphere Zn 2+ -nucleotide complexes is ca. 2 Å and the O-Zn-O angle is ca.…”

Section: Glycosidic Anglementioning

confidence: 99%

Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn²⁺-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate

et al. 2015

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Although involved in various physiological functions, nucleoside bis-phosphate analogues and their metal-ion complexes have been scarcely studied. Hence, here, we explored the solution conformation of 2′-deoxyadenosine- and 2′-deoxyguanosine-3′,5′-bisphosphates, 3 and 4, d(pNp), as well as their Zn(2+)/Mg(2+) binding sites and binding-modes (i.e. inner- vs. outer-sphere coordination), acidity constants, stability constants of their Zn(2+)/Mg(2+) complexes, and their species distribution. Analogues 3 and 4, in solution, adopted a predominant Southern ribose conformer (ca. 84%), gg conformation around C4'-C5' and C5'-O5' bonds, and glycosidic angle in the anti-region (213-270°). (1)H- and (31)P-NMR experiments indicated that Zn(2+)/Mg(2+) ions coordinated to P5' and P3' groups of 3 and 4 but not to N7 nitrogen atom. Analogues 3 and 4 formed ca. 100-fold more stable complexes with Zn(2+)vs. Mg(2+)-ions. Complexes of 3 and 4 with Mg(2+) at physiological pH were formed in minute amounts (11% and 8%, respectively) vs. Zn(2+) complexes (46% and 44%). Stability constants of Zn(2+)/Mg(2+) complexes of analogues 3 and 4 (log KML(M) = 4.65-4.75/2.63-2.79, respectively) were similar to those of the corresponding complexes of ADP and GDP (log KML(M) = 4.72-5.10/2.95-3.16, respectively). Based on the above findings, we hypothesized that the unexpectedly low log K values of Zn(2+)-d(pNp) as compared to Zn(2+)-NDP complexes, are possibly due to formation of outer-sphere coordination in the Zn(2+)-d(pNp) complex vs. inner-sphere in the NDP-Zn(2+) complex, in addition to loss of chelation to N7 nitrogen atom in Zn(2+)-d(pNp). Indeed, explicit solvent molecular dynamics simulations of 1 and 3 for 100 ns supported this hypothesis.

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“…The guanine residues in contrast assume a syn conformation wherein the base closely approaches its sugar. This is the fi rst example of a residue of a natural nucleotide that adopts the syn position in an oligomeric or larger system, although the bases in polynucleotides can be constrained toward this position by a bulky base substituent (116) or by a second covalent linkage between base and sugar (97).…”

Section: B Fo Rm Adopted By Self-complementary Oligodeoxynucleotidesmentioning

confidence: 99%

The Three-Dimensional Structure of DNA

Zimmerman¹

1982

Annu. Rev. Biochem.

188

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This is a particularly interesting time to review the three-dimensional struc tures of DNA. Among recent dramatic events are the demonstration of a radically new type of DNA structure-the left-handed Z-helix-as well as the determination of the detailed structure of a segment of B form DNA. The latter is now especially relevant, as an increasing number of heretical candidates are being proposed to replace several familiar models for DNA, including the Watson-Crick model for the B form. Accordingly, the empha sis of this review is on the regular structures that have been proposed for double-stranded DNA. The review starts by considering two of the ma jor conformations (or "forms") that have been proposed for DNA, namely the B and Z forms, IThe US Government has the right to retain a nonexclusive, royalty-free license in and to any copyright covering this paper.

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Spectroscopic studies on the structure of poly(8‐bromoadenylic acid): Effect of glycosidic torsion angle on the conformation and flexibility in polyribonucleotides

Cited by 17 publications

References 85 publications

Conformational analysis of brominated pA2′‐5′A2′‐5′A analogs

Conformational analysis of brominated pA2′‐5′A2′‐5′A analogs

Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn²⁺-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate

The Three-Dimensional Structure of DNA

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Spectroscopic studies on the structure of poly(8‐bromoadenylic acid): Effect of glycosidic torsion angle on the conformation and flexibility in polyribonucleotides

Cited by 17 publications

References 85 publications

Conformational analysis of brominated pA2′‐5′A2′‐5′A analogs

Conformational analysis of brominated pA2′‐5′A2′‐5′A analogs

Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn2+-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate

The Three-Dimensional Structure of DNA

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Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn²⁺-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate