HLDF-6 peptides exhibit neuroprotective effects in the experimental model of preclinical Parkinson's disease.

The mechanisms of the neuroprotective action of the hexapeptides HLDF-6 encoded by the amino acid sequence 41-46 of Human Leukemia Differentiation Factor and its homoserine derivative HLDF-6H were studied in an experimental 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model of Parkinson's disease (PD). C57Bl/6 mice received two intraperitoneal injections of 18 mg/kg MPTP-HCl, with an interval of 2 hours. MPTP-induced motor dysfunction was assessed using horizontal grid test.

Screening and Behavioral Validation of a Novel Peptide, LCGA-17, With Anxiolytic-Like Properties.

The aim of the study was to develop better anxiolytics and antidepressants. We focused on GABA receptors and the α2δ auxiliary subunit of V-gated Ca channels as putative targets because they are established as mediators of efficacious anxiolytics, antidepressants, and anticonvulsants. We further focused on short peptides as candidate ligands because of their high safety and tolerability profiles.

Pharmacokinetics and Molecular Modeling Indicate nAChRα4-Derived Peptide HAEE Goes through the Blood-Brain Barrier.

One of the treatment strategies for Alzheimer's disease (AD) is based on the use of pharmacological agents capable of binding to beta-amyloid (Aβ) and blocking its aggregation in the brain. Previously, we found that intravenous administration of the synthetic tetrapeptide Acetyl-His-Ala-Glu-Glu-Amide (HAEE), which is an analogue of the 35-38 region of the α4 subunit of α4β2 nicotinic acetylcholine receptor and specifically binds to the 11-14 site of Aβ, reduced the development of cerebral amyloidogenesis in a mouse model of AD. In the current study on three types of laboratory animals, we determined the biodistribution and tissue localization patterns of HAEE peptide after single intravenous bolus administration.

Neurotropic peptide HLDF-6-amide reduces age-related decline in sexual activity in old male rats.

Aging is associated with a decline in the erectile capacity and sexual motivation. Emerging new therapy for the treatment of these age-related pathologies in men is the use of the regulatory peptides. We validated the use of HLDF-6-amide (Thr-Gly-Glu-Hse-His-Arg-NH2) as a potential modulator of sexual performance in aged male rats.

Studying the Specific Activity of the Amide Form of HLDF-6 Peptide using the Transgenic Model of Alzheimer's Disease.

The neuroprotective and nootropic activities of the amide form (AF) of the HLDF-6 peptide (TGENHR-NH) were studied in transgenic mice of the B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) line (the animal model of familial Alzheimer's disease (AD)). The study was performed in 4 mouse groups: group 1 (study group): Tg+ mice intranasally injected with the peptide at a dose of 250 μg/kg; group 2 (active control): Tg+ mice intranasally injected with normal saline; group 3 (control 1): Tg- mice; and group 4 (control 2): C57Bl/6 mice. The cognitive functions were evaluated using three tests: the novel object recognition test, the conditioned passive avoidance task, and the Morris water maze.

Studying the Toxic Effects of Some Biologically Active Peptides on the Model of Mouse Embryonic Stem Cells.

We studied the effects of peptide drugs (HLDF-6, PGP, RPGP, and PGLP) and peptide pharmaceutical products (Semax, Selank, and thyroliberin) on proliferation and survival of mouse embryonic stem cells and their derivatives. Differentiation of mouse embryonic stem cells into neuronal precursors was evaluated. PGP and PGLP in concentrations of 10 and 0.

Interaction of Cholera Toxin B-subunit with Human T-lymphocytes.

In this work, I-labeled cholera toxin B-subunit (CT-B) (specific activity 98 Ci/mmol) was prepared, and its high-affinity binding to human blood T-lymphocytes (K = 3.3 nM) was determined. The binding of the I-labeled CT-B was inhibited by unlabeled interferon-α (IFN-α), thymosin-α (TM-α), and by the synthetic peptide LKEKK, which corresponds to sequences 16-20 of human TM-α and 131-135 of IFN-α (K 0.

Binding of Synthetic LKEKK Peptide to Human T-Lymphocytes.

The synthetic peptide LKEKK corresponding to sequence 16-20 of human thymosin-α1 and 131-135 of human interferon-α2 was labeled with tritium to specific activity 28 Ci/mol. The [3H]LKEKK bound with high affinity (Kd = 3.7 ± 0.

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.

Use of deuterium labeling by high-temperature solid-state hydrogen-exchange reaction for mass spectrometric analysis of bradykinin biotransformation.

Rationale: Studies of molecular biodegradation by mass spectrometry often require synthetic compounds labeled with stable isotopes as internal standards. However, labeling is very expensive especially when a large number of compounds are needed for analysis of biotransformation. Here we describe an approach for qualitative and quantitative analysis using bradykinin (BK) and its in vitro degradation metabolites as an example.

Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer's disease.

A comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide (HLDF-6-OH) and its amide form (HLDF-6-NH2), was conducted. The study was performed in male rats using two models of a neurodegenerative disorder. Cognitive deficit in rats was induced by injection of the beta-amyloid fragment 25-35 (βA 25-35) into the giant-cell nucleus basalis of Meynert or by coinjection of βA 25-35 and ibotenic acid into the hippocampus.

Neurotensin-like peptides as potential antipsychotics: modulation of the serotonin system.

Neurotensin-like peptides acting as functional antagonists of serotonin receptors were revealed in the head-shaking test on mice. The neurotensin-like peptides block the serotonin-induced platelet aggregation in humans. Radioligand binding assay showed that neurotensin-like peptides modulate specifi c binding of 5НТ2 serotonin receptor antagonist ketanserin, but have no effect on binding of ligands of 5HT2c receptor mesulergine and 5HT1а receptors NAN-190.

Autistic children display elevated urine levels of bovine casomorphin-7 immunoreactivity.

Elevated concentrations of circulating casomorphins (CM), the exogenous opioid peptides from milk casein, may contribute to the pathogenesis of autism in children. Because several mass spectrometry studies failed to detect casomorphins in autistic children, it was questioned whether these peptides can be detected in body fluids by mass spec. Here we demonstrated, using a novel high sensitivity ELISA method, that autistic children have significantly higher levels of urine CM-7 than control children.

[Solid state isotope hydrogen exchange for deuterium and tritium in human gene-engineered insulin].

The reaction of high temperature solid state catalytic isotope exchange in peptides and proteins under the action of catalyst-activated spillover hydrogen was studied. The reaction of human gene-engineered insulin with deuterium and tritium was conducted at 120-140° C to produce insulin samples containing 2-6 hydrogen isotope atoms. To determine the distribution of the isotope label over tritium-labeled insulin's amino acid residues, oxidation of the S-S bonds of insulin by performic acid was performed and polypeptide chains isolated; then their acid hydrolysis, amino acid analysis and liquid scintillation counts of tritium in the amino acids were conducted.

Interaction of synthetic peptide octarphin with human blood lymphocytes.

The synthetic peptide octarphin (TPLVTLFK, fragment 12-19 of β-endorphin), a selective agonist of nonopioid β-endorphin receptor, was prepared with specific activity 28 Ci/mmol. The binding of [3H]octarphin to T and B lymphocytes isolated from the blood of donors was studied. It was found that [3H]octarphin binds both to T and B cells with high affinity: Kd = 3.

Synthetic peptide octarphin (TPLVTLFK) inhibits the activity of the hypothalamus-pituitary-adrenal axis through nonopioid β-endorphin receptor.

The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12-19 of β-endorphin, a selective agonist of nonopioid β-endorphin receptor, was labeled with tritium to specific activity of 29 Ci/mmol. The analysis of [(3)H]octarphin binding to rat pituitary and adrenal cortex membranes revealed the existence of one type of binding sites (receptors): Kd 5.9 and 35.

Interaction of the synthetic peptide octarphin with rat adrenal cortex membranes.

The synthetic peptide octarphin (TPLVTLFK, fragment 12-19 of β-endorphin), a selective agonist of the non-opioid β-endorphin receptor, was labeled with tritium yielding specific activity of 28 Ci/mmol. The binding of [3H]octarphin to rat adrenal cortex membranes was studied under normal conditions as well as after cold and heat shocks. It was found that under normal conditions [(3)H]octarphin specifically binds to the membranes with high affinity: K(d1) = 36.

Blood-brain barrier unlocked.

The brain is protected by a physiological blood-brain barrier (BBB) against toxins and some metabolites circulating in the blood. At the same time, the BBB limits penetration into the brain of many neuroactive drugs. Efficient ways to increase BBB permeability for delivery of drugs of different chemical nature into the brain are unknown.

Synthetic peptide TPLVTLFK (octarphin) reduces the corticosterone production by rat adrenal cortex through nonopioid β-endorphin receptor.

The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12-19 of β-endorphin, a selective agonist of nonopioid β-endorphin receptor, was labeled with tritium to a specific activity of 29 Ci/mmol. [(3)H]Octarphin was found to bind to high-affinity naloxone-insensitive binding sites on membranes isolated from rat adrenal cortex (K(d) = 35.7 ± 2.

Interaction of synthetic peptide octarphin with rat myocardium membranes.

A selective agonist of non-opioid β-endorphin receptor synthetic peptide octarphin (TPLVTLFK, specific activity 28 Ci/mmol) was prepared. The [3H]octarphin binding to rat myocardium membranes before and after experimental myocardial infarction (EMI) was studied. It was found that [3H]octarphin with high affinity and specificity binds to non-opioid β-endorphin receptor of rat myocardium membranes before EMI: K(d1) value of the [3H]octarphin specific binding to membranes was 1.

Detection of nonopioid β-endorphin receptor in the rat myocardium.

Two selective agonists of nonopioid β-endorphin receptor, synthetic peptides TPLVTLFK (octarphin) and SLTCLVKGFY (immunorphin), were labeled with tritium to specific activity of 29 and 25 Ci/mmol, respectively. Both labeled peptides were found to bind to high-affinity naloxone-insensitive binding sites on the membranes isolated from the rat myocardium (Kd = 2.0 ± 0.

Immunostimulating effect of the synthetic peptide octarphin corresponding to β-endorphin fragment 12-19.

We have synthesized the peptide TPLVTLFK corresponding to β-endorphin fragment 12-19 (dubbed octarphin) and its analogs (LPLVTLFK, TLLVTLFK, TPLVLLFK, TPLVTLLK, TPLVTLFL). The octarphin peptide was labeled with tritium (specific activity 28 Ci/mol), and its binding to murine peritoneal macrophages was studied. [3H]Octarphin was found to bind to macrophages with high affinity (K(d) = 2.

Binding of synthetic peptide TPLVTLFK to nonopioid beta-endorphin receptor on rat brain membranes.

The synthetic peptide TPLVTLFK corresponding to the sequence 12-19 of beta-endorphin (referred to as octarphin) was found to bind to high-affinity naloxone-insensitive binding sites on membranes isolated from the rat brain cortex (K(d) = 2.6 +/- 0.2 nM).