Indices of acute inflammation against a background of lithium oxybutyrate action

The experiments on rats have shown that intraperitoneal administration of silver nitrate solution induces peritonitis while subplantar histamine, serotonin and prostaglandin E2 administration leads to an acute paw edema. Preliminary subcutaneous injection of lithium hydroxybutyrate prevents the development of inflammation.     

Sequential stimulation of synthesis of two specific cytoplasmic proteins in early estrogen action.

The early effect of administration of estrogen on the synthesis of cytosol proteins in the uterus of the ovariectomized rat was analyzed. A sequential stimulation of two cytoplasmic proteins, having molecular weights of 44,200 and 70,500, was observed. The former protein is probably the IP protein described by Gorski and his colleagues. The latter and larger protein has a molecular weight equivalent to that of a nonhistone chromosomal protein recently described by our laboratory, and may be the cytoplasmic forerunner of that chromosomal protein.     

Mode of action towards oligopeptides and proteins of hydrolase H, a high-molecular-weight aminoendopeptidase from rabbit skeletal muscle

The mode of action towards oligopeptides and proteins of hydrolase H purified from rabbit skeletal muscle was studied. The presence of protamine or alpha-N-benzoylarginine p-nitroanilide (an endopeptidase substrate) changed both the Km and V values of the enzyme towards Leu-beta-naphthylamide (an aminopeptidase substrate). This indicates that the binding site for an endopeptidase substrate is different from that for an aminopeptidase substrate. Hydrolase H as an aminopeptidase displayed broad specificity. The enzyme hydrolyzed various dipeptides readily except the dipeptides containing Pro or an amino acid with a hydrophobic beta-branched chain at the NH2 terminus. Pro and Val at the NH2 terminus of tripeptides were also difficult to release, whereas Ile and Val of tetrapeptides were easily released in contrast with those of dipeptides. The longer the peptide chain of Glyn (n = 2, 3, 4), the more susceptible was it to hydrolase H. Hydrolase H behaved as an endopeptidase only towards protamine among the proteins tested. The other proteins, casein, bovine serum albumin, myofibrils, troponin, hemoglobin, sarcoplasmic proteins, and myoglobin were probably attacked only by the aminopeptidase activity of the enzyme.     

Mechanism of the action of the delta sleep-inducing peptide against a background of L-DOPA administration

A reciprocal nature of the shifts in activity of type A and B monoamine oxidases has been observed under the effect of DSIP against the background of L-DOPA administration (50 micrograms/kg) in the subfractions from the rabbit sensorimotor cortex. The results suggest that the activation of type A monoamine oxidase and serotoninergic system is the basis of the adaptive behavior of animals.     

Abiogenic synthesis of oligopeptides in the open space

Exobiology is a relatively new field of sciences, which was established in connection with the development of the space technology, expanding the range of biological studies beyond the Earth. The major task of exobiology is the study of processes that give rise to the life, biological evolution, and distribution of living creatures in the universe. The term exobiology was introduced by the Dutch researcher Lederberg (1960). During fifty years of progressive development, it turned into a wide interdisciplinary field of sciences, including a number of disciplines, such as astrophysics, organic and analytical chemistry, geology, geochemistry, and other planet sciences not to mention various biological disciplines. Exobiology has become an inherent part of national and international space programs (Carle et al., 1992; Morrison, 2001).     

Monte Carlo docking of oligopeptides to proteins.

A new two-step procedure has been developed for the docking of flexible oligopeptide chains of unknown conformation to static proteins of known structure. In the first step positions and conformations are sampled and the association energy minimized starting from an approximate preselected docking position. The resulting conformations are further optimized in the second step by a Metropolis Monte Carlo minimization, which optimizes each of these structures. The method has been tested on the HIV-1 aspartic proteinase complex with an inhibitor, whose crystallographic structure is known at 2.3 A resolution. Furthermore, the application of this method to the docking of the hendecapeptide 58-68 of the influenza A virus matrix protein to the HLA-A2 molecule produced results which are in agreement with experimental observations in identifying side chains critical for T cell recognition and residues responsible of MHC protein binding.     

Recognition of damaged regions in DNA by oligopeptides and proteins

The binding of various damaged DNAs to the single-strand binding protein coded for by gene 32 from bacteriophage T4, on the one hand, and of oligopeptides containing tryptophan and lysine residues, on the other hand, is described. These molecules exhibit a higher affinity for modified DNA than for native DNA in so far as modification results in a local destabilization of the double-stranded structure of the nucleic acid. Stacking interactions between aromatic amino acids and nucleic acid bases appear to play a crucial role in the recognition of destabilized regions induced by chemical agents (carcinogens and antitumor drugs). These interactions confer to the peptide lysyl-tryptophyl-lysine an endonucleolytic activity specific for apurinic sites. From results obtained with such oligopeptides a model for the active sites of Ap-endonucleases is proposed which could account for the strategy used by the denV endonuclease from phage T4 during the first step of excision repair of pyrimidine dimers in DNA. The effect of the overall conformation of modified DNA on repair efficiency is discussed.     

Protease-catalyzed synthesis of oligopeptides in heterogenous substrate mixtures

A systematic study of enzymatic peptide synthesis in heterogeneous substrate mixtures was carried out, with the aim of establishing the preparative scope of this methodology. Semiliquid eutectics were obtained with various combinations of neutral, acidic, and basic amino acid derivatives, in the presence or absence of adjuvants. A range of serine cysteine, and metalloproteases readily catalyzed the formation of the required dipeptides under these conditions. The synthetic usefulness of the approach was demonstrated by the sequential and convergent synthesis of derivatives of a number of bioactive di-, tri-, and pentapeptides, including aspartame, sweet lysine peptide, kyotorphin amide, ACE-inhibiting and -immunoactive tripeptides, and Leu-enkephalin amide, with overallyields of 21% to 84% and productivities of 0.13 to 0.75 g/g being obtained. (c) 1994 John Wiley & Sons, Inc.     

Differential stimulation by polyamines of phage RNA-directed synthesis of proteins

The effect of polyamines on Q beta and MS2 phage RNA-directed synthesis of three kinds of protein in an Escherichia coli cell-free system has been studied. With both phage RNAs, the degree of stimulation of protein synthesis by spermidine was in the order RNA replicase greater than A protein, while the synthesis of coat protein was not stimulated significantly by spermidine. The synthesis of RNA replicase was stimulated by 1 mM spermidine approx. 8-fold. From the results of Q beta RNA direct alanyl-tRNA and seryl-tRNA binding to ribosomes and initiation dipeptide synthesis, it is suggested that the preferential stimulation of the synthesis of RNA replicase by spermidine is due at least partially to the stimulation of the initiation of RNA replicase synthesis.     

Template-specific stimulation of RNA synthesis by phosphorylated non-histone chromatin proteins

Phosphorylated non-histone chromatin proteins are shown to stimulate the synthesis of RNA in a cell-free system using rat liver RNA polymerase and rat DNA as template. This stimulation is not observed when DNA's of other species are used as template, or when the phosphorylated proteins have been treated with alkaline phosphatase.     

Reproductive success of males of the ICR outbred line during propagation against the background of antigenic stimulation

Diversity of viruses, bacteria, microscopic fungi, and endo- and ectoparasites is an inevitable environmental factor that influences the host reproduction and that is determined not only by negative effects of infectious diseases but also by activation of protective mechanisms, which provide a confrontation to the pressure of parasites. In the present work, hemocyanin was injected into males of the ICR outbred line in order to study reproductive consequences of antigenic stimulation of males. Intact females were added to control and antigen-stimulated males at the initial stage of antibody formation. During 6 days of combined keeping, a significantly greater amount of ovulated egg cells and living embryos were registered in the females added to males that were injected with hemocyanin compared with that theoretically expected for equal reproductive yield. Females covered by antigen-stimulated males bred larger embryos compared with those in the control. Indices of female fertility depended on prevalence of cellular (Th1) or humoral (Th2) immune responses in antigen-stimulated males. Shift of Th1/Th2 balance resulted in higher preimplantation embryonic losses in females covered by males with a prevalence of cellular immune response; however, they bred larger embryos. Thus, it was established that activation of the immune system in males does not influence their reproductive abilities. This allows us, on the one hand, to explain the contribution of protective reactions of the organism in the increase in fertility of the mammals that inhabit territories with high specific abundance of parasites; on the other hand, it demonstrates new ways of the management of the reproduction of animals bred under human control.     

Light-directed simultaneous synthesis of oligopeptides on microarray substrate using a photogenerated acid

Photogenerated acid (PGA) was used as the acid to remove the protection group from amino acids or peptide oligomers. Comparative study of the deprotection using a PGA, trisarylsulfonium antimonyhexafluoride (SSb), and trifluoroacetic acid (TFA) was performed on glass microscope slides. The results showed that PGA can replace TFA in the deprotection step of oligopeptide synthesis with comparable efficiencies. Acids needed for the deprotection step were generated in situ by light activation of the precursor molecule on the microwell substrate. A mask-less laser light illumination system was used to activate the precursor. The accuracy of the amino acid sequence of the synthesized oligopeptide and the location of the synthesis was illustrated by the specific recognition binding of two different models: lead(II) ion-peptide biosensor for lead(II) and human protein p53 (residue 20-25)-mouse MAb DO1. After parallel synthesis of the target peptide models and their analogues based on the predetermined pattern, specific binding treatment, and fluorescence labeling, the fluorescence emission images of the oligopeptide microarray showed fluorescence intensity as a result of specific binding at the correct locations of the array. The stepwise synthesis efficiencies of pentapeptide synthesis on the microwell substrate range are approximately 96-100% and do not decrease with respect to the chain length of the peptide.     

Effect of endogenous oligopeptides and brain-specific proteins on aggressive behavior in the rat

In experiments on non-bred males of white rats, the effect was studied on their aggressive behaviour of intraventricular injections of brain-specific proteins of S-100 group, gamma-globuline fraction from the serum of rabbits immunized by proteines S-100 (gamma S-100) and non-immunized rabbits (gamma-SNK) as well as of angiotensin, bradikinin and saline. S-100 lowered intermales aggressivity and that connected with pain, and had phasic inhibitory effects on rats emotional reactivity. gamma S-100 increased the aggressivity connected with pain, did not affect the intermales aggressivity and phasically raised (as well as gamma-SNK) the emotional reactivity. gamma-SNK, angiotensin and bradikinin did not change these kinds of aggressivity. None of the administered agents influenced the level of rats predetary aggressivity.     

Imitation of neurophysiological effects of long-term sensitization with the action of the blockers of protein synthesis in snailsHelix lucorum

The experiments on command neurons of defensive behavior in snailsHelix lucorum have shown that the synaptic components of responses to the testing stimuli are facilitated within 65 to 75 min after the onset of the application of the protein synthesis inhibitors cycloheximide or anisomycin (30 µM during 30 min) to the central nervous system. At the same time, the parameters of the electrical properties of neuronal membrane (membrane potential level and excitability) were not affected by the blockers. The facilitatory effects were not observed when the blockers were applied for a longer period or when their concentration was raised to 300 µM. The blockade of the responses to different sensory stimuli appeared selective. The facilitation of the responses to tactile stimulation of the head, to weak quinine solution, and to carrot juice lasted for about an hour, 2–3 h and about 1.5 h, respectively. The blockers facilitated only the responses to tactile stimulation of the head, but did not change the responses to stimulation of the middle part of the foot or the mantle bolster. Some characteristics of the blocking effects are similar to those of long-term sensitization. The blocking effects observed are suggested to be due to activation of synthesis of short-living proteins functionally related, in particular, to selective regulation of synaptic transmission.Neirofiziologiya/Neurophysiology, Vol. 26, No. 1. pp. 61–67, January–February, 1994.     

Effect of a viral infection on the cellular chromosome apparatus of mice in vitro and in vivo against a background of hydrocortisone action]

A cytogenetic investigation of murine bone marrow after hydrocortison injection has been made. High doses of hormone (50 mg/kg) provoke deteriorations in bone marrow both in the structure and in the chromosome number. A dose of 5 mg/kg has no such effect. The Koksak A13 virus does not induce cytogenetic deteriorations in mice, however, it is able to produce a big mutagenic effect on the hydrocortison background. The vaccine strain of measles virus -- Leningrad-16 -- also increases its mutagenic action on the bone marrow cell chromsome apparatus of mice affected with hydrocortison. At the same time, in the cell culture of murine kidney, hydrocortison does not induce chromosome deteriorations and even lowers the frequency of cells with deteriorations in the chromosome set during the initial days after injecting the virus culture with measles virus.     

Sequential oligopeptides. Synthesis and characterization of the oligopeptides and a polypeptide with the repeating sequence L-norvalyl-glycyl-L-proline

The synthesis and characterization of a series of oligopeptides (from the tripeptide to the octadecapeptide) with the repeating sequence L -norvalyl-glycyl-L -proline and a polytripeptide with this sequence are reported. The oligomers were synthesized step by step using the mixed anhydride method. All the products were chemically and optically pure. The polymer was prepared by the active ester method, using the p-nitrophenyl ester as the polymerizable tripeptide derivative. Good yield of relatively high average molecular-weight polymer was obtained. In the accompanying paper conformational investigations, both in solution and in the solid state, on the oligomers and the polymer are described.