Regulatory Peptides Research Articles

A proposed mechanism for Vibrio export monitoring polypeptide folding in the ribosome exit tunnel

The ribosome is a fundamental biomolecular complex that produces proteins in cells. The nascent polypeptide chains of newly synthesized proteins are produced deep within the ribosome at the peptidyl-transferase center (PTC) and pass through the ribosomal exit tunnel before they fold into their functional conformations. The Vibrio export monitoring polypeptide (VemP) is a mechano-sensitive regulatory peptide that folds into a helix-loop-helix structure in the ribosome tunnel near the PTC, which causes elongation arrest.

Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models

Alzheimer’s disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal ions and phospholipidic membranes. In particular, Cu2+ ions play a pivotal role in modulating Aβ aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the Aβ:Cu2+ complex are of particular interest. Here we tested the anti-aggregating properties of a heptapeptide, Semax, an ACTH-like peptide, which is known to form a stable complex with Cu2+ ions and has been proven to have neuroprotective and nootropic effects. We demonstrated through a combination of spectrofluorometric, calorimetric, and MTT assays that Semax not only is able to prevent the formation of Aβ:Cu2+ complexes but also has anti-aggregating and protective properties especially in the presence of Cu2+. The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of Aβ:Cu2+ complexes.

The Role of Endogenous Peptides in the Systemic Self-Regulation of Organisms

Regulatory peptides are a wide group of biologically active compounds that affect the current physiological processes in living organisms. Peptides are synthesized in the organism of all biological species, from bacteria to mammals. From a biological point of view, the regulatory peptides have a versatile effect on the organism, they can act as neurotransmitters, neuromodulators, hormones, growth factors, cytokines, etc..The regulatory systems are necessary for all multicellular organisms, to control the function of the cell, to unite it, into one whole organism. In the first half of the 20th century, it was believed that, there were three types of such systems: nervous, immune and endocrine. It was considered that, these systems functioned independently andtheir interaction just was an exceptions. In the 60s of the 20th century, was accumulated enough scientific data, according to which the biologically active peptides were the determining factors of the joint action of the above systems.For today, the physicochemical properties, their specific action, synthetic analogues of physiologically active peptides have been explored.The chemical synthesis of regulatory peptides has been implemented and their therapeutic effects on the human body have been proven.The monograph presents the effect of endogenous peptides on various physiological processes in biological organisms, aslo theirstructural construction and mechanisms of action. In addition, there is discussed, the use and perspectives,of both natural and artificial peptides in medicine.

Boc-Protected Proline-Containing Monoamines as Promising Prodrugs

In recent years, drug designers have increasingly focused on creating complex compounds containing biologically active molecules of various chemical classes in their structure. Such modifications increase the stability of resulting molecules in the organism and increase their ability to achieve the desired targeting effect. Regulatory peptides-based drugs are of particular interest. In this work, we combined the monoamines (serotonin or dopamine) and N-terminal-protected biologically active peptides or amino acids in a single compound and characterized the resulting molecules' enzymatic stability and possible molecular activity. Boc-Pro-5HT and Вос-Pro-DA were stable for at least 180 min of incubation in the presence of PEP, amino-and carboxy-peptidases, as well as blood plasma. This time is enough to reach their corresponding biological targets in the organism and become additional monoamines and regulatory peptides. It was also shown that these complex compounds possess specific targets on cell plasmatic membranes and can affect some neuroreceptor systems (GABA and Ach, in particular) as highly selective allosteric modulators. The above features make these molecules promising candidates for prodrugs and require further research on the mechanisms of their action.

Crosstalk between Acidosis and Iron Metabolism: Data from In Vivo Studies.

Iron absorption requires an acidic environment that is generated by the activity of the proton pump gastric H(+)/K(+)ATPase (ATP4), expressed in gastric parietal cells. However, hepcidin, the iron regulatory peptide that inhibits iron absorption, unexpectedly upregulates ATP4 and increases gastric acidity. Thus, a concept of link between acidosis and alterations in iron metabolism, needs to be explored. We investigated this aspect in-vivo using experimental models of NH4Cl-induced acidosis and of an iron-rich diet. Under acidosis, gastric ATP4 was augmented. Serum hepcidin was induced and its mRNA level was increased in the liver but not in the stomach, a tissue where hepcidin is also expressed. mRNA and protein levels of intestinal DMT1(Divalent Metal Transporter 1) and ferroportin were downregulated. Serum iron level and transferrin saturation remained unchanged, but serum ferritin was significantly increased. Under iron-rich diet, the protein expression of ATP4A was increased and serum, hepatic and gastric hepcidin were all induced. Taken together, these results provide evidence of in-vivo relationship between iron metabolism and acidosis. For clinical importance, we speculate that metabolic acidosis may contribute in part to the pathologic elevation of serum hepcidin levels seen in patients with chronic kidney disease. The regulation of ATP4 by iron metabolism may also be of interest for patients with hemochromatosis.

Discriminative Utility of Apelin-to-NT-Pro-Brain Natriuretic Peptide Ratio for Heart Failure with Preserved Ejection Fraction among Type 2 Diabetes Mellitus Patients.

Background: Apelin is a regulatory vasoactive peptide, which plays a pivotal role in adverse cardiac remodeling and heart failure (HF) with reduced ejection fraction. The purpose of the study was to investigate whether serum levels of apelin is associated with HF with preserved election fraction (HFpEF) in patients with T2DM. Methods: The study retrospectively involved 101 T2DM patients aged 41 to 62 years (48 patients with HFpEF and 28 non-HFpEF patients). The healthy control group consisted of 25 individuals with matched age and sex. Data collection included demographic and anthropometric information, hemodynamic performances and biomarkers of the disease. Transthoracic B-mode echocardiography, Doppler and TDI were performed at baseline. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and apelin were measured by ELISA in all patients at the study entry. Results: Unadjusted multivariate logistic model yielded the only apelin to NT-proBNP ratio (OR = 1.44; p = 0.001), BMI > 34 кг/м2 (OR = 1.07; p = 0.036), NT-proBNP > 458 pmol/mL (OR = 1.17; p = 0.042), LAVI > 34 mL/m2 (OR = 1.06; p = 0.042) and E/e’ > 11 (OR = 1.04; p = 0.044) remained to be strong predictors for HFpEF. After obesity adjustment, multivariate logistic regression showed that the apelin to NT-proBNP ratio < 0.82 × 10−2 units remained sole independent predictor for HFpEF (OR = 1.44; 95% CI: 1.18–2.77; p = 0.001) HFpEF in T2DM patients. In conclusion, we found that apelin to NT-proBNP ratio < 0.82 × 10−2 units better predicted HFpEF in T2DM patients than apelin and NT-proBNP alone. This finding could open new approach for CV risk stratification of T2DM at higher risk of HF.

Cytokine profile of chronic rhinosinusitis without polyps

Chronic rhinosinusitis (CRS) is the most common immunological ENT disease, which has several phenotypes. The heterogeneity of CRS is due to the peculiarities of their pathogenetic mechanisms - the system of cytokines plays the crucial significance. They are biologically active substances and present regulatory peptides that demonstrate an immunomodulatory and regulatory effects not only in the local level but the system level as well. To determine specific features of the cytokine profile in blood serum among patients with CRS without polyps (CRSwP). Serum cytokines (IL-1α, IL-1RA, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, IFN-α2, IFN-γ, GM-CSF) were defined in 75 patients: 32 patients with CRSwP were operated (main group) - 17 with cyst of maxillary sinus, 15 with edema of the maxillary sinuses. The control group - 43 patients were under surgery for a deviated nasal septum (septoplasty). The groups were comparable to gender and age. The cytokines detection rate was different in all groups. IL-4 (detection rate 93.3-95.3%) and IFN-γ (79.1-86.7%) were measured nearly the all groups. IL-8 (73.3-76.5%) and IL-17 (76.5-80.0%) were often measured in the group with CRSwP; in contrast to the control group - these indicators were lower: 60.5% and 65.5%, respectively. IL-1α (82.4%) and IFN-α2 (76.5%) were often detected in CRS with cystic formations. IL-1β, IL-5, IL-7, IL-9, IL-15 were measured in all groups in less than 30% of patients; IL-2 and IL-6 - in the group of CRS with cystic formation; IL-10, IL-12p40, IL-13 in the group with edema of maxillary sinuses. In a quantitative comparison of the concentration of cytokines. Significant differences in concentration of cytokines between the groups were not obtained (p>0.05) in terms of quantity. CRSwP with cystic formation is characterized by the development of T2 type immune response and a higher inflammation-related tissue damage.

Functional characterization of C-TERMINALLY ENCODED PEPTIDE (CEP) family in Brassica rapa L

ABSTRACT The small regulatory C-TERMINALLY ENCODED PEPTIDE (CEP) peptide family plays crucial roles in plant growth and stress response. However, little is known about this peptide family in Brassica species. Here, we performed a systematic analysis to identify the putative Brassica rapa L. CEP (BrCEP) gene family. In total, 27 BrCEP genes were identified and they were classified into four subgroups based on the CEP motifs similarity. BrCEP genes displayed distinct expression patterns in response to both developmental and several environmental signals, suggesting their broad roles during Brassica rapa development. Furthuremore, the synthetic BrCEP3 peptide accelerated Brassica rapa primary root growth in a hydrogen peroxide (H2O2) and Ca2+ dependent manner. In summary, our work will provide fundamental insights into the physiological function of CEP peptides during Brassica rapa development.

Efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of angina pectoris of coronary heart disease (CHD): A protocol for systematic review and meta analysis.

Background:Coronary heart disease (CHD) angina pectoris is a clinical syndrome in which episodic chest pain or chest discomfort is the main manifestation of temporary ischemia and hypoxia of the myocardium due to coronary atherosclerosis and coronary artery functional changes (spasm). A large amount of clinical evidence confirms that acupuncture combined with Chinese herbal medicine in the treatment of CHD and angina pectoris can relieve the symptoms of angina pectoris and improve the performance of electrocardiograph ischemia; It still has obvious therapeutic effects in regulating the levels of cardiovascular regulatory peptides ET and cGRP. To better evaluate the effectiveness and safety of acupuncture combined with Chinese herbal medicine in the treatment of CHD and angina pectoris, we designed a systematic evaluation program to provide a reliable scientific basis for the future use of this method.Methods:Search Pubmed database, Embase, Cochrane library, Chinese Biomedical Literature CD-ROM Database (CBMdisk), China Journal Network Full-text Database (CNKI), Wanfang Database, Web of Science (SCI-E), the retrieval time is established from each database Until October 2021, search for relevant eligible randomized controlled trials with keywords or subject terms “acupuncture”, “Chinese herbal medicine”, and “CHD angina”. Outcome indicators were clinical symptoms of CHD and angina pectoris, changes in electrocardiogram, changes in blood lipids, and significant improvement in traditional Chinese medicine syndromes before and after treatment. Two researchers independently carried out data extraction and quality assessment, and use RevMan5.3 software to carry out final data analysis and assessment.Results:This study provides a reliable clinical scientific basis for acupuncture combined with Chinese herbal medicine for the treatment of CHD and angina pectoris.Conclusion:Acupuncture combined with Chinese herbal medicine can effectively relieve the clinical symptoms of CHD and angina pectoris and improve the performance of electrocardiograph. At the same time, it can reduce the cardiovascular regulatory peptide ET and increase the level of cGRP in the patient's plasma, thus confirming its effectiveness and safety.

СЕМАКС – ПЕРСПЕКТИВЫ ПРИМЕНЕНИЯ (краткое обзорное сообщение)

A brief overview report on the materials of domestic research, as a priority, shows a brief history of the study of regulatory peptides, in particular Semax. The need to continue scientific research in this direction is due, in addition to somatoform and psychosomatic diseases, complications of var-ious diseases in the form of memory impairment, a decrease in the efficiency of mental labor, the appearance of the same symptoms as a manifestation of postcovid syndrome. It is also expected to develop technologies that enhance the effect of neuropeptides by improving the ways of delivering them to the internal environment of the body, including in obstetric and gynecological pathology.

Regulatory Peptides in Asthma.

Numerous regulatory peptides play a critical role in the pathogenesis of airway inflammation, airflow obstruction and hyperresponsiveness, which are hallmarks of asthma. Some of them exacerbate asthma symptoms, such as neuropeptide Y and tachykinins, while others have ameliorating properties, such as nociception, neurotensin or β-defensin 2. Interacting with peptide receptors located in the lungs or on immune cells opens up new therapeutic possibilities for the treatment of asthma, especially when it is resistant to available therapies. This article provides a concise review of the most important and current findings regarding the involvement of regulatory peptides in asthma pathology.

Changes of Gastric Secretion after Bolus and Slow Intravenous Administration of Bombesin and Neurotensin

Objectives:The aim of the present study was to evaluate the changes caused by intravenous administration of regulatory peptides, bombesin (BBS) and neurotensin (NT), on gastric secretion, serum gastrin, and plasma levels of bombesin-1ike immunoreactivity (BLI) and neurotensin. Materials and methods: Fourteen dogs underwent an upper gastrointestinal tract operation and a Pavlov pouch for the concentration of gastric fluids was formed. The experimental animals were divided into two groups. Peptides were given one month after the second operation and after fasting for 12 hours. In group A, the effects of BBS were studied after a rapid 1 ìg/kg body weight dose and a slow 30´ 0.5 ìg/kg body weight dose administration intravenously. Correspondingly to group B the effects of NT were studied in the same way. Results:The rapid intravenous infusion of BBS caused a very significant increase in gastrin levels, BLI in plasma, volume and HCl of the gastric fluids. The same results, plus a significant decrease in gastric pH, were observed following slow intravenous infusion of BBS. Concerning the NT, rapid administration caused a significant decrease in the volume of gastric fluids. Slow NT administration of caused a significant reduction in gastric fluid volume and in HCl. On the contrary, pH was significantly increased. Conclusion:Bombesin increases plasma gastrin levels and HCl secretion. Neurotensin administration causes a decrease in HCl secretion without affecting gastrin levels in plasma.

Relationship between Serum Kallistatin and Afamin and Anthropometric Factors Associated with Obesity and of Being Overweight in Patients after Myocardial Infarction and without Myocardial Infarction.

Extensive clinical and epidemiological evidence has linked obesity to a broad spectrum of cardiovascular disease (CVD), including coronary disease, heart failure, hypertension, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden death. In addition, increasing knowledge of regulatory peptides has allowed an assessment of their role in various non-communicable diseases, including CVD. The study assessed the concentration of kallistatin and afamin in the blood serum of patients after a myocardial infarction and without a cardiovascular event, and determined the relationship between the concentration of kallistatin and afamin and the anthropometric indicators of being overweight and of obesity in these groups. Serum kallistatin and afamin were quantified by ELISA tests in a cross-sectional study of 160 patients who were divided into two groups: study group (SG) (n = 80) and another with no cardiovascular event (CG) (n = 80). Serum kallistatin concentration was significantly higher in the SG (p < 0.001), while the level of afamin was significantly lower in this group (p < 0.001). In addition, a positive correlation was observed in the SG between the afamin concentration and the waist to hip ratio (WHR), lipid accumulation product (LAP) and the triglyceride glucose index (TyG index). In the CG, the concentration of kallistatin positively correlated with the LAP and TyG index, while the concentration of afamin positively correlated with all the examined parameters: body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHtR), visceral adiposity index (VAI), LAP and TyG index. Serum kallistatin and afamin concentrations are associated with the anthropometric parameters related to being overweight and to obesity, especially to those describing the visceral distribution of adipose tissue and metabolic disorders related to excessive fatness.

Erratum to: Analysis of fructose and mannose – regulatory peptides signaling pathway in porcine epithelial oviductal cells (OECs) primary cultured long-term in vitro

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Transfusional Iron Overload in Sickle Cell Patients:Outcomes of Chelation Therapy

Iron (Fe) overload is not rare among sickle cell disease (SCD) patients. It results from either chronic transfusions for primary or secondary stroke prevention, or more commonly sporadic, mostly unnecessary transfusions and are associated with significant morbidity, secondary to hepatic, cardiac and renal Fe deposition. Previous studies at our Center showed that 12% of the adult SCD population had Fe overload, and vast majority of these (80%) resulted from episodic transfusions (Son et al, 2013). Subsequent studies showed that the Fe regulatory peptide, hepcidin was appropriately upregulated in SCD subjects with Fe overload, and the plasma levels of the glycoprotein hormone erythroferrone (ERFE) was not as high as that found in patients with transfusion dependent beta thalassemia (TDT) due to the absence of significant ineffective erythropoiesis in SCD (Thawer et al, 2017, Mangaonkar et al, Brit. J. Haematol, 2020). We report on the utilization and outcomes in Fe overloaded SCD patients who were prescribed the oral chelating agent deferasirox.22 patients were prescribed deferasirox; median age was 38, 12 female 10 male. 21 had Hb SS, and 1 had s-b 0 thalassemia. Deferasirox dose ranged from 720-2500 mg/day (12 to 28 mg/Kg/day). Nonadherence was ascertained by patients' own admission. Figures 1-3 show the pre and post ferritin levels in subjects who were on deferasirox, and in controls; patients who took deferasirox had a more pronounced decrease in their ferritin (p=.004 vs p=.74). Although hepatic MRI for liver iron content (LIC) was not available on all patients, in those who underwent MRI there was a correlation between LIC and serum ferritin obtained at close temporal proximity (Fig. 4). Most common side effects of deferasirox were gastrointestinal (abdominal pain, nausea, vomiting, diarrhea), which were seen less commonly with the newer oral formulation (Jadenu).Several conclusions can be drawn from our observation on relatively small number of patients: 1) Deferasirox is effective in decreasing Fe overload as shown by serum ferritin levels 2) Second generation of oral deferasirox is better tolerated, and therefore is associated with improved adherence, 3) Documentation of a decrease in LIC with chelation will be important for the reversal of Fe induced organ damage, and 4) Parallel studies of the levels of Fe regulatory peptides hepcidin and erythroferrone (ERFE) will clarify the effect of chelation therapy on biomarkers of Fe metabolism. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Влияние пептида His-Phe-Arg-Trp-Pro-Gly-Pro на процессы свободнорадикального окисления в условиях хронического иммобилизационного стресса

Studying the effects of regulatory peptides on the stress-induced shifts in the bodily processes is of great fundamental and applied significance. Currently, a wide range of peptide neurotropic drugs, affecting the stress response development, are used in medicine, and new promising molecules are being studied. The study was aimed to assess the effects of the adrenocorticotropic hormone (ACTH) synthetic analog, ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5, 50 and 500 μg/kg, on the free-radical oxidation processes in Wistar rats, subjected to chronic restraint stress (CRS) during two weeks. Serum levels of 8-oxo-2'-deoxyguanosine (8-OHdG) and superoxide dismutase 3 (SOD3) were assessed by enzyme immunoassay, and the levels of thiobarbituric acid reactive substances (TBARS) were assessed by fluorimetric method. CRS lead to the significant increase in the 8-OHdG levels by 18.4% (p = 0.01) and the decrease in the SOD3 levels by 14.3% (p = 0.01), however, it had no effect on the levels of TBARS. ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5 and 50 μg/kg, significantly decreased the levels of 8-OHdG by 19.8% (p = 0.03) and 30% (p = 0.001), respectively. Thus, it was found that CRS resulted in oxidative stress in animals. ACTH(6-9)-Pro-Gly-Pro administration at a dose of 5 and 50 μg/kg inhibits the stress-induced free-radical oxidation processes.

The Single-Cell Transcriptomic Analysis of Prefrontal Pyramidal Cells and Interneurons Reveals the Neuronal Expression of Genes Encoding Antimicrobial Peptides and Immune Proteins.

The investigation of the molecular background of direct communication of neurons and immune cells in the brain is an important issue for understanding physiological and pathological processes in the nervous system. Direct contacts between brain-infiltrating immune cells and neurons, and the neuromodulatory effect of immune cell-derived regulatory peptides are well established. Several aspects of the role of immune and glial cells in the direct neuro-immune communication are also well known; however, there remain many questions regarding the molecular details of signaling from neurons to immune cells. Thus, we report here on the neuronal expression of genes encoding antimicrobial and immunomodulatory peptides, as well as proteins of immune cell-specific activation and communication mechanisms. In the present study, we analyzed the single-cell sequencing data of our previous transcriptomic work, obtained from electrophysiologically identified pyramidal cells and interneurons of the murine prefrontal cortex. We filtered out the genes that may be associated with the direct communication between immune cells and neurons and examined their expression pattern in the neuronal transcriptome. The expression of some of these genes by cortical neurons has not yet been reported. The vast majority of antimicrobial (~53%) and immune cell protein (~94%) transcripts was identified in the transcriptome of the 84 cells, owing to the high sensitivity of ultra-deep sequencing. Several of the antimicrobial and immune process-related protein transcripts showed cell type-specific or enriched expression. Individual neurons transcribed only a fraction of the investigated genes with low copy numbers probably due to the bursting kinetics of gene expression; however, the comparison of our data with available transcriptomic datasets from immune cells and neurons suggests the functional relevance of the reported findings. Accordingly, we propose further experimental and in silico studies on the neuronal expression of immune system-related genes and the potential role of the encoded proteins in neuroimmunological processes.

The effects of central ghrelin on serum parameters related to energy metabolism in neonatal chicks

BACKGROUND: Ghrelin is a regulatory peptide that has endocrine and metabolic effects in mammalian and birds.OBJECTIVES: The aim of this study was to investigate the possible effects of intracerebroventricular (ICV) injection of ghrelin on the plasma level of some hormones and biochemical indices that are involved in the energy balance of neonatal chicks. METHODS: Intracerebroventricular injection of 20 or 40 pmol ghrelin/individual was done and blood samples were collected from jugular vein, 15 and 30 minutes after the ICV injection ghrelin for measurement of serum parameters. RESULTS: The ICV administration of 20 and 40 pmol ghrelin/individual had no effects at 15 min post-injection, but at 30 min post-injection, the triiodothyronine (T3) level significantly decreased in a dose-dependent manner. The leptin level also declined significantly compared to that of the control group. There were no significant changes in other parameters, including insulin, T4, triglyceride, cholesterol and glucose. CONCLUSIONS: It can be concluded that the changes that occurred in T3 and leptin levels may have been due to the effects of ghrelin on the metabolic rate and food intake (with regard to T3) and the parallel action of ghrelin and leptin (with regard to leptin).

Spatiotemporal organization of enteroendocrine peptide expression in Drosophila

The digestion of food and absorption of nutrients occurs in the gut. The nutritional value of food and its nutrients is detected by enteroendocrine cells, and peptide hormones produced by the enteroendocrine cells are thought to be involved in metabolic homeostasis, but the specific mechanisms are still elusive. The enteroendocrine cells are scattered over the entire gastrointestinal tract and can be classified according to the hormones they produce. We followed the changes in combinatorial expression of regulatory peptides in the enteroendocrine cells during metamorphosis from the larva to the adult fruit fly, and re-confirmed the diverse composition of enteroendocrine cell populations. Drosophila enteroendocrine cells appear to differentially regulate peptide expression spatially and temporally depending on midgut region and developmental stage. In the late pupa, Notch activity is known to determine which peptides are expressed in mature enteroendocrine cells of the posterior midgut, and we found that the loss of Notch activity in the anterior midgut results in classes of enteroendocrine cells distinct from the posterior midgut. These results suggest that enteroendocrine cells that populate the fly midgut can differentiate into distinct subtypes that express different combinations of peptides, which likely leads to functional variety depending on specific needs.

Intranasal Delivery of a Methyllanthionine-Stabilized Galanin Receptor-2-Selective Agonist Reduces Acute Food Intake

The regulatory (neuro)peptide galanin is widely distributed in the central and peripheral nervous systems, where it mediates its effects via three G protein-coupled receptors (GAL1-3R). Galanin has a vast diversity of biological functions, including modulation of feeding behavior. However, the clinical application of natural galanin is not practicable due to its rapid in vivo breakdown by peptidases and lack of receptor subtype specificity. Much effort has been put into the development of receptor-selective agonists and antagonists, and while receptor selectivity has been attained to some degree, most ligands show overlapping affinity. Therefore, we aimed to develop a novel ligand with specificity to a single galanin receptor subtype and increased stability. To achieve this, a lanthionine amino acid was enzymatically introduced into a galanin-related peptide. The residue’s subsequent cyclization created a conformational constraint which increased the peptide’s receptor specificity and proteolytic resistance. Further exchange of certain other amino acids resulted in a novel methyllanthionine-stabilized galanin receptor agonist, a G1pE-T3N-S6A-G12A-methyllanthionine[13–16]-galanin-(1–17) variant, termed M89b. M89b has exclusive specificity for GAL2R and a prolonged half-life in serum. Intranasal application of M89b to unfasted rats significantly reduced acute 24 h food intake inducing a drop in body weight. Combined administration of M89b and M871, a selective GAL2R antagonist, abolished the anorexigenic effect of M89b, indicating that the effect of M89b on food intake is indeed mediated by GAL2R. This is the first demonstration of in vivo activity of an intranasally administered lanthipeptide. Consequently, M89b is a promising candidate for clinical application as a galanin-related peptide-based therapeutic.