Nikolai F. Myasoedov

SPECIFIC EFFECTS OF HEAVY NUCLEI IN CHEMICAL EQUILIBRIUM

The article reports the results of numerical estimations of the nuclear size equilibrium isotope effects for some medium-weight and heavy elements obtained by using the following equation: ln α fs (i,j) = (kT)−1Δρ(0)z −1 f(z)⟨r 2⟩ij, where α fs (i,j) are the equilibrium isotope separation factors corresponding to the nuclear size contribution of the nucleus field-shift for a given pair of isotopes i and j; Δρ(0) is the difference of the nucleus electron density for a pair of compounds; z −1 f(z) is the tabulated nuclear charge (z) function characterizing the nucleus of the element being the same for all isotopic nuclei; δ⟨r 2⟩ ij is the isotopic shift of the nucleus effective charge radius in square for the isotopes i and j, and k is the Boltzmann constant. The values Δρ(0) were determined from either theoretical or experimentally determined isotope field shifts and from the data of Mossbauer spectroscopy. The ⟨r 2⟩ ij values were taken from experimental measurements followed by their standardization. The values of α fs (i,j) increase from Fe to U and achieve sufficiently high level for lanthanides. For heavier elements, these specific isotope effects begin to exceed the classical chemical equilibrium isotope separation factors.

[Semax and selank inhibit the enkephalin-degrading enzymes from human serum]].

Dose-dependent effect of synthetic heptapeptides Semax (Met-Glu-His-Phe-Pro-Gly-Pro) and Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) on the enkephalin-degrading enzymes of human serum was demonstrated. The inhibitory effects of Semax (IC5010 μM) and Selank (IC5020 μM) are more pronounced than that of puromycin (IC5010 mM), bacitracin, and some other inhibitors of peptidases. Beside the heptapeptides, their pentapeptide fragments also possessed an inhibitory effect; tri-, tetra- and hexapeptide fragments did not display such an effect. As the above enzymes take part in degradation of not only enkephalins but also other regulatory peptides, it can be assumed that one of the mechanisms of biological activity of Semax and Selank is related to this inhibitory activity of theirs.

Synthesis of physiologically active tritiated compounds using high specific activity tritiated water

A number of physiologically active compounds—steroid hormones, some phytohormones, carbohydrates and nicotinamide adenine dinucleotide—have been tritiated using high specific activity tritiated water produced by the oxidation of tritium gas on palladium oxide and in the presence of a dry organic solvent. In the process the effect of various variables such as catalyst and solvent have been investigated. The products so obtained had specific activities in the range 3–25 Ci/mmol. Copyright

QUANTUM-STATISTICAL AND PHENOMENOLOGICAL ANALYSIS OF EQUILIBRIUM ISOTOPE EFFECTS

This article discusses theoretical consequences of quantum-statistical representations of logarithm of isotopic reduced partition function ratio (ln β). Among the effects being under consideration are the localization of equilibrium isotope effect on the molecular structural elements in the vicinity of the site of isotopic substitution, distribution of increments of ln β, relationship between ln β values for the substitution of different atoms, and the influence of anharmonicity. The review also presents the phenomenological analysis of ln β for more than 2000 compounds as well as the classification of equilibrium isotope effects according to the causes of their appearance. Methods for the quantitative statistical estimation of the maximum possible isotope separation factors and criteria for the purposeful search for chemical exchange systems applicable for the practical separation of isotopes are also given.

Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice

This study is focused on a new amide derivative of the peptide HLDF-6 (Thr-Gly-Glu-Asn-His-Arg). This hexapeptide is a fragment of Human Leukaemia Differentiation Factor (HLDF). It displays a broad range of nootropic and neuroprotective activities. We showed, for the first time, that the peptide HLDF-6-amide has high anxiolytic activity. We used ‘open field’ and ‘elevated plus maze’ tests to demonstrate anxiolytic effects of HLDF-6-amide (0.1 and 0.3 mg/kg intranasally), which were comparable to those of the reference drug diazepam (0.5 mg/kg). Five daily equipotent doses of HLDF-6-amide selectively mitigated anxiety and increased the density of NMDA receptors in the hippocampus of stress-susceptible BALB/c mice, and had no effect on stress-resilient C57BL/6 mice. The subchronic administration of HLDF-6-amide showed no effect on the density of GABAA and nicotine receptors but was accompanied by a nonselective decrease of the 5-HT2A serotonin receptor density in frontal cortex of both strains. The mechanism of the specific anxiolytic activity of HLDF-6-amide may include its action on the NMDA-glutamatergic receptor system of the hippocampus and on serotonin 5-HT2A-receptors in the prefrontal cortex. The psychotropic activity of HLDF-6-amide is promising for its introduction to medical practice as a highly effective anxiolytic medicine for mental and neurological diseases.

Serine decomposition in solid-state catalytic isotope exchange of a peptide

Abstract In connection with work related to cAMP-dependent protein kinase, a tritiated substrate, Arg-Arg-Ala-Ser-Val-Ala, was prepared from the corresponding unlabeled peptide by solid-state catalytic isotope exchange. Varying amounts of side products with chromatographic properties very similar to those of the substrate were observed. Careful chromatographic comparison with a complete set of diastereomers eliminated racemization as the reason for this heterogeneity. Instead, the serine residue was identified as the major source of by-products, presumably due to primary elimination of water followed by saturation of the dehydroalanine residue, transforming it into a racemic alanine, thus giving rise to Arg-Arg-Ala-( d, l -Ala)-Val-Ala.

Systemic N-terminal fragments of adrenocorticotropin reduce inflammation- and stress-induced anhedonia in rats

Emerging evidence implicates impaired self-regulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammation as important and closely related components of the pathophysiology of major depression. Antidepressants show anti-inflammatory effects and are suggested to enhance glucocorticoid feedback inhibition of the HPA axis. HPA axis activity is also negatively self-regulated by the adrenocorticotropic hormone (ACTH), a potent anti-inflammatory peptide activating five subtypes of melanocortin receptors (MCRs). There are indications that ACTH-mediated feedback can be activated by noncorticotropic N-terminal ACTH fragments such as a potent anti-inflammatory MC1/3/4/5R agonist α-melanocyte-stimulating hormone (α-MSH), corresponding to ACTH(1-13), and a MC3/5R agonist ACTH(4-10). We investigated whether intraperitoneal administration of rats with these peptides affects anhedonia, which is a core symptom of depression. Inflammation-related anhedonia was induced by a single intraperitoneal administration of a low dose (0.025mg/kg) of lipopolysaccharide (LPS). Stress-related anhedonia was induced by the chronic unpredictable stress (CUS) procedure. The sucrose preference test was used to detect anhedonia. We found that ACTH(4-10) pretreatment decreased LPS-induced increase in serum corticosterone and tumor necrosis factor (TNF)-α, and a MC3/4R antagonist SHU9119 blocked this effect. Both α-MSH and ACTH(4-10) alleviated LPS-induced anhedonia. In the CUS model, these peptides reduced anhedonia and normalized body weight gain. The data indicate that systemic α-MSH and ACTH(4-10) produce an antidepressant-like effect on anhedonia induced by stress or inflammation, the stimuli that trigger the release of ACTH and α-MSH into the bloodstream. The results suggest a counterbalancing role of circulating melanocortins in depression and point to a new approach for antidepressant treatment.

New concepts of the mechanism of hydrogen exchange between organic molecules and strong acidic centers

Ab initio calculations of the activation energy of the reaction of hydrogen exchange between the methane molecule and the H3O+ ion in the gaseous phase have been carried out by using Hartree-Fock methods and Moeller-Plesset second order perturbation theory (MP2) methods. The structure of the transition state of this reaction has been found. The interaction of the H3O+ ion with molecules of aliphatic hydrocarbons and amino acids has been studied by the Serniernpirical AMI method.