[Synthesis of somatostatin in Escherichia coli cells: isolation and characteristics].

A synthetic gene coding for somatostatin-14 (SST) was cloned in plasmid expression vectors in frame with the chloramphenicol acetyl transferase (CAT) gene, both genes being divided by a Met residue. The hybrid gene was expressed under the control of the CAT gene promoter (Pcat) or the tryptophan operon promoter (Ptrp). Them fused genes gave insoluble polypeptide products amounting from 5% of the total cellular protein under constitutive biosynthesis conditions (Pcat) to 30% upon induction (Ptrp).

[The antioxidant activity of cyclohistidylproline].

A cyclohistidyl-proline, cyclopeptide possessing a hormonal and neurotrophic activity is shown to be an inhibitor of the (Fe + ascorbic acid)-induced peroxidation of membrane lipids, its effect being dependent on its concentration. Inhibition of the malondialdehyde formation by cyclohistidil-proline is accompanied by protection of the membrane bound Ca-pump. In the test of the free radical cumole oxidation antioxidative effect of cyclohistidyl-proline is 4 times higher than that of the hydrophilic antioxidant carnosine.

[Conformation-activity relations of dermorphin and its pentapeptide analogs].

Low-energy peptide backbone structures of dermorphin (DM), amide of its N-terminal pentapeptide (DM 1-5) and DM 1-5 analogues with substitutions of Gly4 for Leu, D-Gln, Aal or Tal were determined by energy calculations. The above analogues were shown to possess different affinities toward opiate receptors of mu-type. The comparison of low-energy backbone structures of DM, DM 1-5 and its analogues resulted in development of the dermorphin "biologically active" conformation being characteristic of its binding with mu-type receptors.

[Analgesic activity of nucleoamino acid analogs of neuropeptides injected intracisternally and intravenously in mice].

The antinociceptive activity of several enkephalin and kyotorphine analogues having nonproteinogenic nucleoamino acids: adenyl alanine, thyminyl alanine or uracilyl alanine in their structure was studied by the method of tail clip stimulation in mice. Kyotorphine and its analogues administered intracisternally to mice were found to inhibit the nociceptive responses only at doses similar to toxic ones. At the same time among nucleoamino acid analogues of enkephalins compounds were detected which possessed the antinociceptive activity not only at intracisternal administration but at intravenous injection as well.

[The electrographic picture of sleep as affected by a thyroliberin analog].

The neurotropic effects of pyroglutamyl-seryl-phenylalanine amide, the thyrotropin-releasing hormone analog, have been studied in experiments on male rats. Electrodes were implanted in the hippocamp and the optic cortex for registration of electroencephalograms. The analog administered intraperitoneally decreased the time of onset of slow sleep increasing the duration of this phase.

[Properties of (Ala5, Orn9)-somatostatin. The inhibition of pancreatic and hypophyseal hormone secretion in cell culture].

Ability of Ala5, Orn9-somatostatin to inhibit the secretion of insulin, glucagon, somatotropic hormone (STH) and prolactin was tested on the model of primary monolayer culture of isolated insular pancreatic and adenohypophyseal cells. Chemical substitution performed between positions 5 and 9 in somatostatin molecule failed to change essentially hormone's biologic activity in suppression of insulin and glucagon in the culture of pancreatic insular cells isolated from newborn rats. Somatostatin analog revealed its natural hormonal ability to inhibit STH secretion but failed to affect that of prolactin.

[Response of the secretory glands of the stomach to peptide injection into the hypothalamus, caudate nucleus and amygdala].

In chronic experiments on dogs, microapplication of neurotensin into the hypothalamus or amygdala combined with histamin or pentagastrin stimulation of the stomach secretory function significantly reduced the stomach secretion. Microapplication of somatostatin into the hypothalamus or amygdala combined with i.v.

[Interaction of tripeptides containing arginine and tyrosine (or phenylalanine) residues with synthetic polynucleotides and DNA of various origins].

Model peptides--L-Arg-Gly-L-Arg, L-Arg-L-Tyr-L-Arg and L-Arg-L-Phe-L-Arg bind to different DNAs and synthetic polynucleotides and are found in the major groove of the double helix. Polynucleotide complexes containing L-Arg-Gly-L-Arg were studied in order to consider the influence of the arginine residues on the polynucleotide melting temperature. It was shown, that L-Arg-L-Tyr-L-Arg and L-Arg-L-Phe--L-Arg lowers the melting temperature in all polynucleotides studied.

[Biological properties of structural analogs of thyroliberin].

Effects of 8 synthetic tripeptides--structural analogues of thyroliberin (TRH)--in basal and TRH-induced secretion of prolactin (PRL) and thyrotropin (TSH) were studied in primary cultures of rat pituitary cells. 7 tripeptides had chemical structure Pyr-Ser-X-NH2, where X was Leu, Val, Asn, Ala, Ile, Met, Phe. One tripeptide had the structure Pyr-Ser-Gly-OCH3.

[A new structural analog of human insulin--glycine-B30-insulin].

Enzymatic-chemical preparation of glycine-B30-insulin, a new structural analog of human insulin has been performed. The new analog differs from the natural hormone by a substituted ThrB30 residue in the glycine residue. The biological activity of the glycine-B30-insulin as measured by the mouse convulsion assay is 100%.

[Natural peptides and their analogs. XXXV. Synthesis and properties of [Ala5, Orn9]somatostatin].

A total chemical synthesis of [Ala5, Orn9]somatostatin has been performed. This structural analogue of natural somatostatin inhibits the release of somatotropin, insulin and glucagon, but shows no inhibitory effect on secretion of prolactin.

[Effect of thyroliberin on pancreatic islet cell function in rats].

A study was made of the TRH effect on insulin and glucagon secretory function of a 4-day neonatal rat pancreatic islet cell culture. The TRH effect was determined in the range of 10-1000 ng/ml concentrations within 30 min and 3 h of cell cultivation with the hormone. TRH stimulated insulin and glucagon secretion within the range of the above doses.

[Synthetic tripeptide miniluliberin and its biological activity].

The effects of the synthetic decapeptide LH-RH and tripeptide mini LH-RH on LH and FSH secretion were compared. Experiments on ovariectomized female rats receiving estradiol benzoate and progesterone showed that i. v.

[Aspartame--the sweet-tasting dipeptide--does not affect the pancreatic insulin-secreting function].

The action of a synthetic dipeptide aspartam (150 to 180 times as sweet as glucose) on pancreatic insulin-secretory function of rats was studied in vivo and in vitro. The drug was given orally while drinking (300 mg/kg body weight) or was added to the incubation medium of cultivated pancreatic cells (20 mM). It was shown that insulin content in the rat blood serum remained unchanged 10 and 35 minutes after aspartam administration.

[A new structural analog of human insulin-- [glutamine-B30] insulin].

A new structural analogue of human insulin, [glutamine-B30]insulin, has been prepared by enzymatic-chemical means. This analogue differs from natural hormone by substitution of the ThrB30 residue. Biological activity of the [glutamine-B30]insulin is 100% in the mouse convulsion assay.

[Biologically active fragments of protein hormones].

As shown in a number of experiments, corticotropin-like and opiate hormones are synthesized in a body as high molecular protein precursors, involving their biologically-active fragments. Pharmacological properties and perspectives for practical use of somatotropin fragments, synthetic opiate peptides as well as the peptides active in stimulation of pancreatic hormones secretion are considered in details.

[Functional state of the thyroid and its regulatory system in tumor-bearing animals].

A comparative study of labelled thyroxine and iodine accumulation was carried out in the thyroid endocrine complex under endoliquor and intraabdominal introduction of thyrotropic hormone (TTH) and thyrotropin-releasing-factor (TRF) in rats with transplantable and induced tumours as well as in intact animals. A sharp decrease of the system response to TRF in tumour-bearing animals was established. The incorporation of labelled thyroxine introduced into the thyroid gland tissue and posterior region of the hypothalamus is found to be lower under the tumour growth.

[Effect of somatostatin on gastric hydrochloric acid secretion and serum gastrin concentration in the dog].

I.v. administration of somatostatin (1.

[Natural peptides and their analogs. XXXI. Synthesis and properties of the retro-analog of methionine-5-enkephalin].

The synthesis of retro-analog of methionine-5-enkephalin was performed. This peptide is an isomer of the natural methionine-5-enkephalin, but differs from it by opposite direction of peptide linkages between the amino acid residues. The influence of retro-analog on prolactin secretion was studied both in vivo and in vitro.

[Effect of methionine-5-enkephalin retroanalog on gastric secretion].

Alteration of the enkephalin molecule by means of synthesis of peptide with opposite direction of peptide connections between residues of aminoacids (retro--methionin--5--enkephalin) entailed some changes of its action in respect to activity of the stomach secretory cells in dogs. Thus, for instance, the retroanalogue methionin--5--enkephalin proved to be a more efficient activator of gastric secretion induced with pentagastrin.

[Influence of thyroliberin and its analogs with different hormonal activity on the pharmacological effects of ethanol].

TRH and its two analogs with modified hormonal activity were examined for the capacity to antagonize acute and chronic effects of ethanol in mice. It has been demonstrated that L-pyroglutamyl-L-seryl-L-leucinamide, an analog of TRH, that does not affect the secretion of TSH and decreases prolactin production has the same capacity as TRH to reduce the time of ethanol narcosis but produces a lesser effect on the ethanol-induced fall of rectal temperature. Both the drugs did not affect the ethanol-altered ability of mice to hold on the rotating bar.

[Chronic action of the fat-mobilizing fragment of human somatotropin on the fat content of fat depots and the plasma glucose level in rabbits].

The effect was studied of synthetic tetradecapeptide-the fat-mobilizing human somatotropin fragment 31-34--on the fat content in fat depot and glucode concentration in the rabbit blood plasma and urine. A marked decrease in subcutaneous (the nape region), perirenal, mesenteric and epididimal fat content, accompanied by partial replacement of the fatty tissue by the connective one, was seen 3 to 4 weeks after tetradecapeptide injection to rabbits. Peptide effect manifested itself only under condition of the inadequate diet and was especially pronounced in young animals.

[Sensitivity of hypothalamic neurons to beta-endomorphin, met-enkephalin, and thyroliberin].

A study was made of susceptibility of hypothalamic neurons to beta-endorphine, thyroliberin and met-enkephalin applied microiontophoretically. The opioids were shown to exert a primarily unidirectional effect on the same neurons irrespective of the fact that the inhibitory action of beta-endorphine was more pronounced. The nalorphine-competitive antagonist of the opiates removed the met-enkephalin-induced inhibition.