Self-association of nucleotides

The self-association of nucleosides decreases within the series adenosine>guanosine>inosine>cytidine ≈uridine. The same trend is observed for the corresponding nucleotides, though less pronounced, as the charge effect governs series like adenosine ? AMP^2?>ADP^3??ATP^4?. Protonation of adenosine considerably reduces its self-stacking tendency: this is different with ATP^4?, where a maximum is reached for H₂(ATP)^2? caused by additional ionic interactions in the [H₂(ATP)]₂ ^4? dimer. Metal ion coordination may promote self-association, e.g., of ATP^4? via (mainly) charge neutralization (Mg²⁺) and the formation of intermolecular bridges in dimeric stacks (Zn²⁺, Cd²⁺). These results allow definition of conditions with negligible self-association and thus the determination of the stability and structure of monomeric nucleotide complexes in aqueous solution, e.g., quantification of macrochelate formation in M(ATP)^2? complexes. Some biological implications of the results are indicated.     

Cyclic nucleotides

The natural occurrence of cyclic nucleotides in higher plants, formerly a topic of fierce debate, is now established, as is the presence of nucleotidyl cyclases and cyclic nucleotide phosphodiesterases capable of their synthesis and breakdown. Here we describe the significant properties of cyclic nucleotides, also outlining their second messenger functions and the history of plant cyclic nucleotide research over its first three decades. Findings of the last five years are detailed within the context of the functional role of cyclic nucleotides in higher plants, with particular emphasis upon nucleotidyl cyclases and cyclic nucleotide-responsive protein kinases, -binding proteins and -gated ion channels, with future objectives and strategies discussed.     

Saturation of anti cyclic nucleotides antibodies by endogenous cyclic nucleotides.

Rabbits immunized against cyclic AMP or cyclic GMP produce antibodies which are fully saturated by their respective endogenous cyclic nucleotides. This was proved a) in comparing radioimmunological measurements of cyclic nucleotides in antiserum and the binding site concentration determined by equilibrium dialysis, b) in showing the ineffectiveness of serum phosphodiesterase to hydrolyze the cyclic AMP present in the anti-cyclic AMP antiserum. Immunological and radioimmunological implications of this phenomenon are discussed.     

Phosphodiesterase of cyclic nucleotides

Problems are considered on form multiplicity, purification and molecular weight of cyclic nucleotides phosphodiesterase. A supposition is made that the molecular weight of the catalytic subunit of the enzyme for most studied objects is about 60000. The catalytic subunit may form di- and trimers and be associated with regulatory proteins of different type. The problem of phosphodiesterase regulation is analyzed on the basis of potentialities of the equilibrium shift between the protein subunits of the enzyme; the role of cyclic nucleotides as well as of triphosphonucleotides are shown to influence the regulation of the enzymic activity. In some cases the mechanism of changes in the activity of phosphodiesterase bound with the receptor is shown to be similar to that for adenylate cyclase. In particular, the role of GTP and one of the protein subunits of phosphodiesterase in this process is stated.     

The prebiotic chemistry of nucleotides

Diiminosuccinonitrile (DISN), formed by the oxidation of diaminomaleonitrile (DAMN), has been investigated as a potential prebiotic phosphorylating agent. DISN effects the cyclization of 3-adenosine monophosphate to adenosine 2, 3-cyclic phosphate in up to 39% yield. The mechanism of this reaction was investigated. The DISN-mediated phosphorylation of uridine to uridine monophosphate does not proceed efficiently in aqueous solution. The reaction of DISN with uridine-5-phosphate and uridine results in the formation of 2,2-anhydronucleotides and 2,2-anhydronucleosides respectively, and other reaction products resulting from an initial reaction at the 2- and 3-hydroxyl groups. The clay mineral catalysis of the cyclization of adenosine-3-phosphate was investigated using homoionic montmorillonites.     

Conformational search of antisense nucleotides

A preliminary MMFF implementation of selenium atom parameters necessary to model the nucleoside 1 is reported. X-ray structures of two compounds 1 and 2 have been used as references. Ab initio methods have been adopted for checking torsional energy profile and charge distribution. Monte Carlo calculations and energy minimization in solvation complete the conformational search.     

Platinum complexes of nucleotides.

The reaction of [Pt(dien)Cl1Cl (dien = NH2CH2CH2NHCH2CH2NH2) with nucleotides has been studied by nuclear magnetic resonance. It has been found that the CMP (cytidine 5'-monophosp-ate) and GMP (guanosine 5'-monophosphate/coordinate to the platinum atom through N3 and N7, respectively. The reaction of the platinum salt with the nucleotide is complete when one to one ratio of platinum to nucleotide is used and no evidence of phosphate group binding to platinum has been found. No additional binding sites have been detected except the N7 site on the guanylic group of GMP even in the presence of a large excess of [Pt(dien) Cl1Cl. The AMP (adenosine 5'monophosphate] coordinates to the platinum at the N1 and/or N7 sites. The reaction of AMP and platinum is complete is complete at a ratio of four platinum to one AMP.     

Lactoferrin interacts with nucleotides

Lactoferrin (LF) is an iron-binding glycoprotein found predominantly in milk and in granulocytes. LF is extremely polyfunctional protein some biological functions of which are determined by its capacity to bind iron, but many other functions are iron-independent. In this article we show for the first time that LF interacts with a number of various mononucleotides.     

Binding of nucleotides to parvalbumins

Intrinsic fluorescence and equilibrium dialysis studies have shown that ATP and ADP bind to parvalbumin molecules with affinities allowing the complex formation at physiological concentrations of protein and nucleotides. The stoichiometry and association constants for the nucleotide binding to calcium-loaded, magnesium-loaded and metal free whiting parvalbumin are different. The data obtained suggest a possible functional significance of the nucleotide-parvalbumin interaction.     

Uridine nucleotides in brain

—Two uridine nucleotides, UDPG and UDPGA, have been measured in brain by a procedure whereby they are extracted from tissue with subsequent utilization, either directly with (UDPGA) or after dehydrogenation (UDPG), in a glucuronidation reaction with harmol or harmalol as cosubstrate. The concentrations of UDPG and UDPGA in brains of a few species of animals examined are, respectively, 11.5–23.3 μmoles/100 g and 0.7–2.5 μmoles/100 g tissue. The ratios of UDPGA to UDPG range from 4% to 11%. The role and importance of these uridine nucleotides in brain are discussed.