Conformation of cyclic .beta.-adenosine 3',5'-phosphate in solution using the lanthanide shift technique

Abstract

The preferred conformation of cyclic 8-adenosine 3',5'-phosphate in aqueous solution has been determined from shifts of proton magnetic resonance signals caused by lanthanide ions. The conformation of the ribose and phosphate groups is consistent with the structure in the crystalline state. At pD 5.3, the purine base is in the syn conformation, with the best agreement (R = 0.048) of calculated and observed shifts at a glycosyl torsion angle of 86°. Reasonable error limits for the torsion angle determination are ±22°. Experiments were performed over a pD range of 2.2-5.3 with a nucleotide concentration range of 0.02-0.072 M, and a lanthanide nucleotide ratio ranging from 0 to 15, without significant changes in the association constant of the lanthanidenucleotide complexes. Keq at pD 5.3,13.0 ± 1.7, and at pD 2.2, Keq = 14.2 ± 2.9. Avery versatile hormonal messenger is cyclic 8-adenosine 3',5'-phosphate (3',5'-AMP).1 2 The crystal structure of 3',5'-AMP shows two molecules in the asymmetric unit which have very different orientations of the purine about the glycosyl bond.3 In one mole-(1) (a) Presented in part at the 29th Southwest Regional Meeting of the American Chemical Society, El Paso, Texas, Dec 1973. (b) Colorado State University, (c) Los Alamos Scientific Laboratory.(2) G.

Lanthanide(III) Complexes of Novel Mixed Carboxylic‐Phosphorus Acid Derivatives of Diethylenetriamine: A Step towards More Efficient MRI Contrast Agents

“…The pH values reported for H 5 L 3 were corrected for the deuterium effect by using the relationship pD = pH + 0.4. [54] A drop of tBuOH (d = 1.2 ppm) was added to the samples as internal reference for 1 H. The assignment of the backbone hydrogen atoms was done by using selective 1 Hdecoupled 13 C NMR spectroscopy for the free ligands and COSY spectra for [La(L 3 )(H 2 O)] 2À . The calculations were performed by using the computer programs Micromath Scientist, version 2.0 (Salt Lake City, UT, USA) or OPIUM.…”

Determination of the syn-anti Equilibrium of Some Purine 3':5'-Nucleotides by Nuclear-Magnetic-Relaxation Perturbation in the Presence of a Lanthanide-Ion Probe

“…The error in our data is at most f 15 % but this corresponds to only a small variation in the relative synlanti contributions. By comparison the results obtained from shift data [7,8] at this pH are not easily reconciled with calculated data.…”

“…In the 3' : 5'-monophosphates the movement of the ribose protons changing from 3E to 4E conformations relative to the metal ion is very small. In the two lanthanide-shift studies 3E [7] and 3T4 [8] conformations were inferred. However, calculations show that neither shift nor relaxation measurements are sufficiently sensitive to give an accurate picture of the ribose Metal-ion-induced changes in the relaxation times corresponding to the bound environment (TI ,2 M ) -l at 28 "C for nucleotides (0.02 M conformation from consideration of the ribose protons alone.…”

“…The conformations of the purine 3' : 5'-nucleotides have been studied by optical rotatory dispersion [l], interpretations of NMR coupling constants [2,3] and chemical shifts [4], potential energy calculations [5,61 and lanthanide-induced shifts in the NMR proton resonances [7,8]. Two crystal structure analyses have been undertaken, on cyclic AMP [9] and cyclic IMP (M. Sundaralingham, personal communication).…”

Conformational transformation coupled with the order–disorder phase transition in 2-methyl-1,3-cyclohexanedione crystals

“…The changes in molecular dimensions (Dunitz, 1995;Braga, 1992), tautomeric forms (Ogawa et al, 1998;Konno et al, 1989), electron transfers (Torrance et al, 1981), polymerization (Yalpani et al, 1983(Yalpani et al, , 1985 etc. equally concern the crystals built from small molecules, large biopolymers (Kroon-Batenburg et al, 1986, isolated molecules (Warshel & Karplus, 1974) or solutions (Lawalle & Zeltman, 1974). In certain cases the crystals may undergo thermodynamic phase transitions which involve transformations of the molecules or ions themselves (Herbstein, 1996;Baudour, 1996;Na È ther et al, 1996;Richardson et al, 1990;Yang et al, 1989;Byrn et al, 1972;Hazen et al, 1987;Ohashi, 1998).…”