RPEP-02708 · 2015Among multiple designed variants, peptides I.2 (RWQWRWQWR, a 9-amino-acid linear peptide) and I.4 (a branched tetravalent structure containing the RRWQWR sequence) showed the strongest activity. Against E. coli ATCC 25922, MIC values ranged from 4-33 μM; against E. faecalis ATCC 29212, MIC values were 10-33 μM.
These short synthetic peptides performed comparably or better than the full lactoferricin protein and longer derivative peptides like II.1 (15 amino acids) and IV.1 (24 amino acids). The common feature of the most active peptides was the RWQWR motif, suggesting this sequence is the core pharmacophore responsible for antibacterial activity. The peptides were synthesized with high yield and purity using standard solid-phase methods.
León-Calvijo, María A; Leal-Castro, Aura L; Almanzar-Reina, Giovanni A; Rosas-Pérez, Jaiver E; García-Castañeda, Javier E; Rivera-Monroy, Zuly J ·
RPEP-02711 · 2015Microneedle pretreatment of human skin enabled dramatic GHK-Cu permeation: 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper crossed the skin in 9 hours, versus essentially zero through intact skin. The depth and percentage of microneedle penetration were directly correlated with application force, which determined the degree of permeability enhancement. Histological assays and confocal microscopy confirmed well-defined channels through the stratum corneum. No skin irritation was observed.
Li, Hairui; Low, Yong Sheng Jason; Chong, Hui Ping; Zin, Melvin T; Lee, Chi-Ying; Li, Bo; Leolukman, Melvina; Kang, Lifeng ·
RPEP-02712 · 2015The researchers successfully synthesized the complete 165-amino-acid human interferon alpha-2b protein using native chemical ligation (NCL), which joins peptide fragments through chemical bonds at cysteine residues. The synthetic IFNα2b retained its biological properties.
This synthesis is an enabling step for mirror-image phage display — a technique where a D-amino acid version of the target protein is used to screen for L-peptide binders, which are then converted to D-peptide versions that resist protease degradation. The ultimate goal is to discover proteolysis-resistant D-peptide antagonists that block IFNα signaling.
Li, Jing; Lehmann, Clara; Chen, Xishan; Romerio, Fabio; Lu, Wuyuan ·
RPEP-02716 · 2015The GHRP-6-biotin conjugate significantly increased myogenic marker proteins, insulin-like growth factor-1 (IGF-1), and collagen type I expression in cultured myoblasts. It also enhanced metabolic activity, indicated by elevated ATP, lactate levels, and enzymatic activities of lactate dehydrogenase and creatine kinase, suggesting stimulation of muscle cell differentiation and energy metabolism.
Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo ·
RPEP-02719 · 2015The review synthesizes current understanding across several areas:
- Collagen structure varies with source and season, affecting extraction conditions and applications
- Fish collagen and gelatin are gaining interest as alternatives to mammalian sources due to safety (BSE/prion concerns) and religious considerations
- Collagen-derived peptides generated through hydrolysis have demonstrated bioactivities in both in vitro and in vivo models
- Beyond nutritional value, collagen peptides may exert biological effects on extracellular matrix cells through food-derived peptides after ingestion
- Applications span food, pharmaceutical, cosmetic, and biomedical industries
- Novel applications continue to emerge for collagen and gelatin products
Liu, Dasong; Nikoo, Mehdi; Boran, Gökhan; Zhou, Peng; Regenstein, Joe M ·
RPEP-02720 · 2015In the MPTP mouse model of Parkinson's disease, 14 days of daily liraglutide (25 nmol/kg) and lixisenatide (10 nmol/kg) treatment prevented:
- Motor impairment on Rotarod, open-field locomotion, and catalepsy tests
- Reduction of tyrosine hydroxylase (TH) levels — the enzyme needed for dopamine production — in the substantia nigra and basal ganglia
- Pro-apoptotic signaling (reduced BAX, increased Bcl-2)
Exendin-4 at 10 nmol/kg showed no protective effects, suggesting the newer, longer-acting GLP-1 drugs have superior neuroprotective properties at comparable doses.
Liu, W; Jalewa, J; Sharma, M; Li, G; Li, L; Hölscher, C ·
RPEP-02721 · 2015Short synthetic self-assembling peptides are ideal bioinks for 3D bioprinting because they naturally form nanofibrous hydrogels that mimic the extracellular matrix — the scaffold that surrounds cells in living tissue. These peptide gels keep cells alive, maintain their normal function, and respond to stimuli (temperature, pH) to gel on demand.
Key advantages for bioprinting: tunable mechanical strength (can be adjusted for different tissue types), excellent shape retention after printing, biocompatibility for implantation, biodegradability, and easy chemical customization. Their short length makes them simple and cheap to synthesize compared to protein-based bioinks.
Loo, Yihua; Hauser, Charlotte A E · Review
RPEP-02723 · 2015Five circulating biomarkers — substance P (a neuropeptide), soluble CD40 ligand, TIMP-1, malondialdehyde, and fragmented cytokeratin-18 — have been identified as prognostic indicators of mortality in traumatic brain injury patients. Each biomarker reflects a different pathway of secondary brain injury: substance P indicates neuroinflammation, sCD40L reflects coagulation and inflammation, TIMP-1 relates to neuroinflammatory matrix remodeling, MDA marks oxidative damage, and CK-18 fragmented signals apoptotic cell death.
Substance P, a tachykinin family neuropeptide synthesized in the central and peripheral nervous system, exerts proinflammatory effects through binding to neurokinin-1 receptors, making it a particularly relevant peptide biomarker in brain injury.
Lorente, Leonardo ·
RPEP-02728 · 2015Chronic treatment with ghrelin and its synthetic analog GHRP-6 significantly increases growth hormone release from bovine pituitary somatotropes, associated with an increase in Na+ macroscopic current. This effect is abolished by tetrodotoxin, indicating involvement of TTX-sensitive Na+ channels NaV1.1 and NaV1.2, whose transcript levels are upregulated by ghrelin and GHRP-6.
Magdaleno-Méndez, Adasue; Domínguez, Belisario; Rodríguez-Andrade, Araceli; Barrientos-Morales, Manuel; Cervantes-Acosta, Patricia; Hernández-Beltrán, Antonio; González-Ramírez, Ricardo; Felix, Ricardo ·
RPEP-02730 · 2015Sleeve gastrectomy patients showed significantly different gut peptide hormone profiles compared to both morbidly obese and non-obese groups:
- Lowest ghrelin concentrations (the primary hunger-stimulating peptide)
- Higher early postprandial cholecystokinin (CCK) peaks — a satiety peptide
- Higher early postprandial glucagon-like peptide 1 (GLP-1) peaks — a satiety and insulin-stimulating peptide
- Accelerated gastric emptying compared to both control groups
- Improved insulin resistance pattern compared to morbidly obese patients
- Reduced hunger and increased satiation scores
Interestingly, no differences in hunger and satiation were observed between morbidly obese and non-obese groups before surgery, suggesting the hormonal changes after surgery drive the appetite effects rather than stomach size alone.
Mans, Esther; Serra-Prat, Mateu; Palomera, Elisabet; Suñol, Xavier; Clavé, Pere ·
RPEP-02731 · 2015N-methylated cis-peptide bonds appear to be a key structural feature that enables cyclic peptides to cross the intestinal barrier. Among 13 N-methylated cyclic pentaalanine peptides tested, those containing cis-peptide bonds showed the highest intestinal permeability in Caco-2 cell models. This structural feature is shared by known orally available cyclic peptides like cyclosporine A. The study also found that enantiomeric pairs (mirror-image peptides) had different permeabilities, strongly suggesting that absorption involves specific carrier-mediated transport pathways rather than simple passive diffusion, especially for polar peptide scaffolds.
Marelli, Udaya Kiran; Ovadia, Oded; Frank, Andreas Oliver; Chatterjee, Jayanta; Gilon, Chaim; Hoffman, Amnon; Kessler, Horst · In Vitro
RPEP-02732 · 2015The researchers tested enantiomeric pairs of five cyclic hexapeptides (three polar, two lipophilic) using two permeability assays. In the PAMPA assay (which measures only passive diffusion through an artificial membrane), all enantiomeric pairs showed identical permeability, as expected for mirror-image molecules with the same physical properties.
However, in the Caco-2 cell model (which contains biological transport machinery), the polar enantiomeric peptides showed significantly different permeability in both apical-to-basolateral and basolateral-to-apical directions. One lipophilic pair also showed differences, while the second lipophilic pair showed equivalent permeability. This discrepancy between PAMPA and Caco-2 results provides the first evidence that carrier-mediated transporters contribute to intestinal peptide absorption, particularly for polar peptides.
Marelli, Udaya Kiran; Bezençon, Jacqueline; Puig, Eduard; Ernst, Beat; Kessler, Horst ·
RPEP-02737 · 2015Using fluorescence correlation spectroscopy and patch-clamp electrophysiology, the researchers demonstrated that dynorphins accumulate in the plasma membrane and induce transient increases in ionic conductance consistent with the formation of giant (~2.7 nm diameter) unstructured, non-ion-selective membrane pores.
Critically, the potency of different dynorphin variants to porate membranes correlated with their known pathogenic effects in cellular and animal models of neurodegeneration. This establishes membrane poration as a probable mechanism for dynorphin-mediated pathological signal transduction, neuronal excitation, and cell death.
Maximyuk, O; Khmyz, V; Lindskog, C-J; Vukojević, V; Ivanova, T; Bazov, I; Hauser, K F; Bakalkin, G; Krishtal, O ·
RPEP-02740 · 2015Proenkephalin knockout (PENK KO) mice showed reduced feeding motivation — fewer licking bouts for sucrose but normal bout lengths — and had lower baseline body weight on regular chow and attenuated weight gain on an energy-dense cafeteria diet.
β-endorphin-deficient (BEND KO) mice showed altered taste reward — shorter licking bouts (suggesting reduced palatability) but normal bout frequency. Critically, BEND KO mice were insensitive to shifts in sucrose concentration and hunger state, indicating β-endorphin specifically mediates orosensory reward responses under conditions of high need or high stimulus value.
PENK KO but not BEND KO mice showed resistance to diet-induced obesity, demonstrating that enkephalins — not β-endorphin — are the primary opioid peptides regulating body weight through motivational tone.
Mendez, Ian A; Ostlund, Sean B; Maidment, Nigel T; Murphy, Niall P ·
RPEP-02742 · 2015Cyclotides have emerged as powerful tools in drug discovery through two principal approaches: (1) as scaffolds in which bioactive peptides can be grafted to improve stability, oral bioactivity, and binding to G-protein coupled receptors (GPCRs), and (2) as natural combinatorial peptide libraries for screening. Their unique circular structure with a cystine knot makes them exceptionally stable compared to linear peptides.
Mollica, Adriano; Costante, Roberto; Stefanucci, Azzurra; Novellino, Ettore ·
RPEP-02746 · 2015Dexamethasone exposure leads to a time-dependent decrease in substance P (SP) mRNA and protein levels in human tendon fibroblasts via glucocorticoid receptor signaling, without affecting the SP receptor NK1R. It also inhibits SP induction by IL-1β and mechanical loading.
Mousavizadeh, Rouhollah; Backman, Ludvig; McCormack, Robert G; Scott, Alex ·
RPEP-02753 · 2015All three tachykinin peptides (SP via NK1R, NKA via NK2R, NKB via NK3R) induced gonadotropin release in adult male and ovariectomized estradiol-replaced female mice. This effect was abolished in Kiss1r knockout mice, proving kisspeptin-dependence.
Sex-specific differences emerged: the NK2R agonist decreased LH in ovariectomized females without estradiol, while the NK1R agonist increased it — contrasting with the NK2R/NK3R pattern. Receptor mapping showed ~50% of arcuate Kiss1 neurons expressed NK1R and 100% expressed NK3R, while NK2R was absent from all kisspeptin and GnRH neurons. Tac1 (SP/NKA) expression was inhibited by estradiol but did not colocalize with Kiss1 mRNA.
Navarro, Víctor M; Bosch, Martha A; León, Silvia; Simavli, Serap; True, Cadence; Pinilla, Leonor; Carroll, Rona S; Seminara, Stephanie B; Tena-Sempere, Manuel; Rønnekleiv, Oline K; Kaiser, Ursula B ·
RPEP-02754 · 2015Diet-induced obesity caused complete ghrelin resistance in mice — peripheral ghrelin injections failed to increase food intake, suppress oxygen consumption, activate the vagus nerve, or trigger signaling in the hypothalamus. The mechanism: a high-fat diet reduced ghrelin receptor expression in both the nodose ganglion (vagus nerve relay station) and the hypothalamus.
Critically, this resistance was driven by inflammation. The high-fat diet triggered activation of macrophages and microglia and upregulated inflammatory cytokines in both the nodose ganglion and hypothalamus, blunting ghrelin's ability to signal through the vagal afferent pathway that normally carries hunger signals from gut to brain.
Naznin, Farhana; Toshinai, Koji; Waise, T M Zaved; NamKoong, Cherl; Md Moin, Abu Saleh; Sakoda, Hideyuki; Nakazato, Masamitsu · Animal Study
RPEP-02755 · 2015Incretin-based therapies — GLP-1 receptor agonists and DPP-4 inhibitors — offer unique advantages for type 2 diabetes management: low hypoglycemia risk, effective postprandial glucose control, and weight reduction (GLP-1 RAs). Short-acting GLP-1 RAs primarily target post-meal glucose spikes, while long-acting formulations provide sustained blood sugar lowering. DPP-4 inhibitors work by preventing the breakdown of natural GLP-1 peptide. Safety considerations include pancreatitis risk, C-cell hyperplasia concerns, renal effects, and GI side effects (especially in older adults).
Neumiller, Joshua J ·
RPEP-02757 · 2015Researchers developed a new way to build ring-shaped (macrocyclic) peptides directly on solid-phase synthesis supports. The key innovation is that the ring closure creates a secondary amine in the peptide backbone that remains chemically reactive — meaning you can keep building on the peptide after cyclization. This enabled the synthesis of both cyclic and bicyclic peptides ranging from 3 to 13 amino acids, and the method was demonstrated by making lipidated antimicrobial peptide variants.
Oddo, Alberto; Münzker, Lena; Hansen, Paul R · Methodology
RPEP-02764 · 2015The HPLC method achieved excellent linearity with a correlation coefficient of 0.9999 and could detect KPV at concentrations as low as 0.01 μg/mL (LOD) and quantify it at 0.25 μg/mL (LOQ). Accuracy and precision tests showed relative standard deviation values below 2%. Under stress conditions (acid, alkali, and hydrogen peroxide), KPV degraded primarily into lys-pro-diketopiperazine, identified by mass spectrometry. The method successfully separated KPV from both its degradation products and endogenous skin components.
Pawar, Kasturi R; Mulabagal, Vanisree; Smith, Forrest; Kolli, Chandra S; Rangari, Vijaya K; Babu, R Jayachandra ·
RPEP-02765 · 2015Chronic administration of the GLP-1 receptor agonists liraglutide (0.3 mg/kg/day) and exenatide (10 μg/kg/day) for four weeks significantly improved trabecular bone mass, connectivity, and structural parameters in ovariectomized (OVX) mice — a standard model of postmenopausal osteoporosis. However, no effect was seen on cortical bone or bone formation in vivo.
Importantly, GLP-1 receptors were found to be expressed in bone marrow cells, osteoclasts, osteoblasts, and osteocytes, indicating that GLP-1 RAs may act directly on bone tissue. Exenatide increased serum calcitonin (which inhibits bone resorption) and decreased sclerostin (which inhibits bone formation), suggesting complex modulation of bone metabolism.
Pereira, M; Jeyabalan, J; Jørgensen, C S; Hopkinson, M; Al-Jazzar, A; Roux, J P; Chavassieux, P; Orriss, I R; Cleasby, M E; Chenu, C · Animal
RPEP-02766 · 2015Ghrelin — the hunger hormone produced mainly by the stomach — doesn't just make you hungry, it makes food taste better by activating the brain's reward system. Ghrelin receptors are found not only in hypothalamic areas that control energy balance, but also in the ventral tegmental area (VTA), where the brain's dopamine-driven reward pathways originate. By targeting mesoaccumbal dopamine neurons, ghrelin connects the gut directly to reward circuitry, creating a physiological link between hunger and the pleasurable experience of eating. Importantly, ghrelin's effects on food reward are overlapping with but distinct from its effects on food intake.
Perello, M; Dickson, S L · Review
RPEP-02771 · 2015All tachykinins and tachykinin receptors examined were found to be locally synthesized in the uterus of early pregnant rats (Days 1-9). Substance P, neurokinin B, and receptors NK1R and NK3R showed major expression changes during the days surrounding implantation.
These peptides and receptors were widely distributed in implantation sites and were particularly abundant in decidual cells — the maternal cells that nourish and support the early embryo. Previous work by the same group showed that blocking the NK3R receptor reduced litter size in rats, supporting a functional role for these peptides in reproduction.
Pinto, Francisco M; Bello, Aixa R; Gallardo-Castro, Manuel; Valladares, Francisco; Almeida, Teresa A; Tena-Sempere, Manuel; Candenas, Luz ·
RPEP-02773 · 2015Propionate — a short-chain fatty acid produced by gut bacteria when they ferment dietary fiber — triggered the simultaneous release of both GLP-1 and PYY (two appetite-suppressing peptide hormones) from the colon in rats and mice. This effect was mediated through the free fatty acid receptor 2 (FFA2): when the researchers repeated the experiments in mice genetically engineered to lack FFA2, propionate's ability to stimulate gut hormone release was significantly impaired both in isolated cell cultures and in live animals.
The study confirmed this through multiple approaches: propionate stimulated GLP-1 and PYY secretion from cultured colon cells, and when infused directly into the colon of live rodents, it elevated both hormones in portal vein and jugular vein blood.
Psichas, A; Sleeth, M L; Murphy, K G; Brooks, L; Bewick, G A; Hanyaloglu, A C; Ghatei, M A; Bloom, S R; Frost, G · Animal Study
RPEP-02776 · 2015Intra-articular administration of ropivacaine microparticle suspensions significantly reduced pain, histological inflammation, and levels of cytokines IL-18 and IL-1β, as well as substance P, compared to both oral and intra-articular celecoxib in a rat arthritis model.
Rabinow, Barrett; Werling, Jane; Bendele, Alison; Gass, Jerome; Bogseth, Roy; Balla, Kelly; Valaitis, Paul; Hutchcraft, Audrey; Graham, Sabine ·
RPEP-02778 · 2015Di-peptide and di-retro-peptide derivatives of human lactoferricin (hLFcin) achieved up to 100% cancer cell toxicity at 20 μM concentration across melanoma (A375), glioblastoma (U-87mg), and rhabdomyosarcoma cell lines. Compared to the parent hLFcin sequence, derivatives showed 10-fold increased toxicity on melanoma and 2-3-fold on glioblastoma.
Structural analysis revealed a critical insight: peptides with loop structures selectively killed cancer cells via apoptosis (confirmed by caspase 3/7 activation, apoptotic blebbing, and DNA fragmentation), while peptides with α-helical structures without loops killed non-specifically through rapid membrane lysis (necrosis). Phosphatidylserine — uniquely exposed on cancer cell surfaces — was identified as the primary membrane target for cancer-selective peptides. Other negatively charged molecules (sialic acid, heparan/chondroitin sulfate) had minor impact on activity.
Riedl, Sabrina; Leber, Regina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar ·
RPEP-02780 · 2015Key age- and sex-dependent findings on peptide control of reproductive hormones:
- Neurokinin B (via NK3R agonist senktide) stimulated FSH secretion in both male and female prepubertal rats
- Adult female rats showed LH but not FSH responses to senktide; adult males showed neither
- Blocking dynorphin with nor-binaltorphimine restored LH responses in adult males and FSH responses in adult females
- Basal LH and FSH levels increased when dynorphin was blocked in adult males
- Substance P and neurokinin A also stimulated gonadotropins prepubertally but had reduced effects in adults
- Dynorphin and its receptor (κ-opioid receptor) gene expression was higher in prepubertal males than females in the mediobasal hypothalamus
Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M ·
RPEP-02781 · 2015A comprehensive review of bovine milk proteins identified numerous peptide sequences with potential anticancer activity. Using the AntiCP prediction server, researchers found that caseins and whey proteins contain a remarkable number of peptide fragments predicted to have antitumor properties. Proline dominated at key positions in casein-derived anticancer peptides, while lysine was prominent in whey-derived ones.
These bioactive peptides can be naturally released during gastrointestinal digestion or through fermentation processes used in making yogurt, cheese, and other dairy products. While the epidemiological evidence linking dairy consumption to cancer risk remains inconsistent, the peptide-level data suggests milk proteins are a promising source of natural anticancer candidates.
Sah, B N P; Vasiljevic, T; McKechnie, S; Donkor, O N · Review
RPEP-02783 · 2015GHRH antagonists potentiate the efficacy of chemotherapy agents such as doxorubicin, docetaxel, 5-FU, irinotecan, and cisplatin by reducing tumor growth, inflammatory signaling, drug resistance gene expression, cancer stem-cell markers, and efflux pump function in various cancer models including triple negative breast cancer, non-small cell lung cancer, and colorectal cancer.
Schally, Andrew V; Perez, Roberto; Block, Norman L; Rick, Ferenc G ·
RPEP-02791 · 2015Intracerebroventricular leptin increased lumbar sympathetic nerve activity (LSNA), heart rate, and mean arterial pressure in anesthetized rats. Inhibiting the paraventricular nucleus with muscimol completely reversed all of leptin's effects, confirming this brain region as essential.
The mechanism involves three parallel pathways converging on the paraventricular nucleus: (1) increased glutamatergic excitatory drive, (2) increased melanocortin 3/4 receptor activation by α-melanocyte-stimulating hormone, and (3) withdrawal of tonic neuropeptide Y inhibitory inputs from the arcuate nucleus. Critically, the melanocortin excitatory effect only manifested when neuropeptide Y Y1 receptor signaling was simultaneously blocked, revealing a gating mechanism where neuropeptide Y withdrawal is required for melanocortin activation to drive sympathetic output.
Shi, Zhigang; Li, Baoxin; Brooks, Virginia L ·
RPEP-02792 · 2015The ghrelin receptor agonist RM-131 significantly accelerated gastric emptying in patients with type 1 and type 2 diabetes and delayed gastric emptying. RM-131 also reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) scores among type 1 diabetic patients. Earlier intravenous administration of TZP-101 showed symptom improvement, but oral TZP-102 did not confirm these effects.
Shin, Andrea; Wo, John M ·
RPEP-02799 · 2015This review synthesizes evidence that growth hormone-releasing hormone (GHRH) treatment significantly reduces visceral fat, improves dyslipidemia, and lowers cardiovascular risk markers in both HIV-infected patients and individuals with general obesity. The underlying mechanism involves a vicious cycle: excess visceral fat suppresses GH secretion (through hyperinsulinemia, elevated free fatty acids, increased somatostatin tone, and reduced ghrelin), and low GH further promotes visceral fat accumulation due to decreased lipolysis. GHRH breaks this cycle by restoring endogenous basal and pulsatile GH secretion without altering pulse frequency — a more physiological approach than direct GH injection.
Stanley, Takara L; Grinspoon, Steven K ·
RPEP-02805 · 2015Semax (Met-Glu-His-Phe-Pro-Gly-Pro), an ACTH4-10 analog with a C-terminal Pro-Gly-Pro extension, demonstrated:
- Formation of three distinct copper(II) complex species
- At pH 5 and above, the predominant species [CuLH-2]2- features 4-nitrogen planar coordination around copper
- Two minor species [CuL] and [CuLH-1]- coexist at pH 3.6-5
- Significant reduction of copper-induced cytotoxicity in:
- SH-SY5Y neuroblastoma cells (brain neuron model)
- RBE4 endothelial cells (blood-brain barrier model)
- Protection assessed by MTT cell viability assay
This reveals that Semax’s neuroprotective activity may partly operate through metal ion chelation rather than solely through receptor-mediated signaling.
Tabbì, Giovanni; Magrì, Antonio; Giuffrida, Alessandro; Lanza, Valeria; Pappalardo, Giuseppe; Naletova, Irina; Nicoletti, Vincenzo Giuseppe; Attanasio, Francesco; Rizzarelli, Enrico ·
RPEP-02807 · 2015Mice lacking the VPAC2 receptor (which responds to the neuropeptides VIP and PACAP) developed much more severe autoimmune brain inflammation (EAE, the animal model for multiple sclerosis). Without VPAC2 signaling, the immune system shifted dramatically toward inflammation: pro-inflammatory Th1/Th17 responses were increased (TNF-α, IL-6, IFN-γ, IL-17), while protective Th2 and regulatory T cell (Treg) responses were reduced (IL-10, TGFβ, IL-4).
Most strikingly, Treg cells — the immune system's brakes — were both fewer in number and functionally impaired in VPAC2-deficient mice. This demonstrates that the VPAC2 receptor is essential for maintaining the pool of Tregs that prevent autoimmune attacks.
Tan, Yossan-Var; Abad, Catalina; Wang, Yuqi; Lopez, Robert; Waschek, James · Animal Study (Knockout Mouse Model)
RPEP-02815 · 2015The review highlights recent technological and chemical advancements in peptide design that enable targeting of intracellular protein-protein interactions, a class of targets traditionally considered undruggable by small molecules or biologics.
Tsomaia, Natia ·
RPEP-02819 · 2015In a double-blind crossover study of 41 adolescents (14 lean, 12 obese insulin-sensitive, 15 obese insulin-resistant):
Baseline: acyl-ghrelin was highest in lean and lowest in obese insulin-resistant (OIR) (P=0.02)
After glucose: ghrelin suppression was similar in lean and obese insulin-sensitive (OIS) but significantly lower in OIR (P=0.03 vs lean)
After fructose: ghrelin suppression differences were more pronounced — lean vs OIS P=0.008, lean vs OIR P<0.001. OIS teens became significantly hungrier after fructose (P=0.015)
PYY: not significantly different at baseline, varied minimally after glucose, but rose after fructose across groups
The pattern reveals a progressive impairment: OIS shows fructose-specific ghrelin suppression failure, while OIR shows failure with both sugars.
Van Name, Michelle; Giannini, Cosimo; Santoro, Nicola; Jastreboff, Ania M; Kubat, Jessica; Li, Fangyong; Kursawe, Romy; Savoye, Mary; Duran, Elvira; Dziura, James; Sinha, Rajita; Sherwin, Robert S; Cline, Gary; Caprio, Sonia ·
RPEP-02821 · 2015In heart failure patients, muscle wasting (sarcopenia) affects roughly 20% and full-body wasting (cachexia) affects under 10% of ambulatory patients. The review establishes a 'wasting continuum' where skeletal muscle is lost before fat tissue — meaning sarcopenia can be an early warning sign that cachexia is coming.
Multiple peptide-based therapies show potential to halt this wasting process: ghrelin and its analogs stimulate appetite and preserve muscle, growth hormone and testosterone promote anabolism, and myostatin antibodies block the signals that tell muscle to break down. Exercise training, essential amino acids, and electrical muscle stimulation are also discussed as complementary approaches.
von Haehling, Stephan · Review
RPEP-02822 · 2015Endostatin — a 20-kDa peptide fragment naturally derived from type XVIII collagen — is one of the most potent known inhibitors of angiogenesis (new blood vessel formation). This review synthesizes a decade of research showing that endostatin works through multiple mechanisms: it binds to several different receptors, inhibits both blood vessel and lymphatic vessel growth, and can suppress cancer metastasis. The paper highlights endostatin's emerging role as both a disease biomarker (abnormal levels correlate with various diseases) and a potential therapeutic agent, particularly in short peptide form.
Walia, Amit; Yang, Jessica F; Huang, Yu-Hui; Rosenblatt, Mark I; Chang, Jin-Hong; Azar, Dimitri T · Review
RPEP-02824 · 2015Rat IAPP (rIAPP) differs from human IAPP at six positions and is a natural amyloid inhibitor — a 'β-breaker' that combines a recognition element with structural features that prevent β-sheet formation. Pramlintide was engineered by introducing rIAPP's three proline substitutions into human IAPP, making it more human-like than rIAPP while still unable to form amyloid.
Comparison of rIAPP, pramlintide, and designed hIAPP analogues revealed that effective peptide-based amyloid inhibitors require a balance: too much similarity to hIAPP risks co-aggregation, while too many disrupting substitutions reduce the ability to recognize and bind the target. Pramlintide represents a well-calibrated compromise between these competing requirements.
Wang, Hui; Ridgway, Zachary; Cao, Ping; Ruzsicska, Bela; Raleigh, Daniel P ·
RPEP-02825 · 2015Chronic psychological stress in mice delayed hair growth by prolonging the telogen (resting) phase and postponing the next growth phases. Stress increased oxidative damage markers (lipid peroxidation) while reducing protective antioxidant enzymes (SOD and GSH-Px) in skin tissue. It also elevated autophagy markers LC3-II and Beclin-1 in the skin. Blocking the substance P receptor with RP67580 restored antioxidant enzyme activity, reduced oxidative damage, lowered autophagy markers, and normalized the hair cycle. The antioxidant Tempol produced similar protective effects. This is the first evidence linking substance P, oxidative stress, and autophagy together in stress-induced hair growth disruption.
Wang, Lei; Guo, Ling-Ling; Wang, Lin-Hui; Zhang, Guo-Xing; Shang, Jing; Murao, Koji; Chen, Deng-Feng; Fan, Xiang-Hua; Fu, Wen-Qing ·
RPEP-02826 · 2015Substance P-deficient mice (TAC1 knockout) had significantly reduced microglial density in the substantia nigra compared to wild-type mice, despite no difference in microglial proliferation rates. Substance P dose-dependently attracted microglia in trans-well migration assays. The chemotactic mechanism required both the NK1 receptor (NK1R) and NADPH oxidase (NOX2), connected by protein kinase Cδ (PKCδ). Genetic ablation or pharmacological inhibition of either NK1R or NOX2 attenuated substance P-induced microglial migration. High levels of substance P were detectable in the substantia nigra as early as postnatal day 1, with microglial density peaking around postnatal day 30.
Wang, Qingshan; Oyarzabal, Esteban; Wilson, Belinda; Qian, Li; Hong, Jau-Shyong ·
RPEP-02828 · 2015Substance P (specifically the selective NK-1 agonist [Sar9, Met(O2)11]-SP) protected MES23.5 dopaminergic cells from MPP+-induced toxicity through multiple mechanisms:
- Prevented MPP+-triggered apoptosis (programmed cell death)
- Decreased MPP+-induced calcium (Ca2+) influx into cells
- Reduced caspase-3 reactivity (a key enzyme in the cell death cascade)
- Lowered reactive oxygen species (ROS) production
- Preserved mitochondrial membrane potential (preventing mitochondrial collapse)
- Inhibited phosphorylation of JNK and p38 MAP kinase (stress-activated signaling pathways)
All protective effects were abolished when the NK-1 receptor antagonist SR140333B was co-administered, confirming that substance P's neuroprotection is mediated specifically through NK-1 receptors.
Wang, Shuang-Yan; Chen, Lei; Xue, Yan; Xia, Yu-Jun ·
RPEP-02829 · 2015In 144 rats randomized to four groups, treatment with thymosin alpha-1 (26.7 µg/kg IV) after SAP induction produced significant improvements:
Survival: Mortality reduced from 50% (6/12) in untreated SAP to 25% (3/12) with TA1 treatment
Immune function: Significantly increased CD3+, CD4+, and CD8+ T-cells and improved CD4+/CD8+ ratio compared to untreated SAP
Inflammatory markers: Significantly lower levels of AST, LDH, α-amylase, P-type amylase, lipase, procalcitonin, TNF-α, IL-4, IL-5, and IL-18 within the first 24 hours (all P<0.05)
Histology: Significantly reduced pancreatic and lung tissue damage on histological scoring
IFNα treatment (4.0×10⁵ U/kg) showed similar benefits, reducing mortality to 33.3% (4/12)
Wang, Xiaoqin; Zeng, Xiaoyan; Yang, Bo; Zhao, Shan; Chen, Wei; Guo, Xuan ·
RPEP-02830 · 2015Ghrelin injected into the paraventricular nucleus (PVN) at doses of 0.03, 0.08, and 0.24 nM dose-dependently accelerated small intestinal transit (SIT) in rats. This effect was systematically dissected:
- GHSR antagonist (D-Lys3-GHRP6, 1 nM) competitively inhibited ghrelin's excitatory effect on SIT and interdigestive myoelectric complex (IMC) activity
- NPY neutralization in the PVN using anti-NPY immunoglobulin also diminished the excitatory effect on IMC
- Peripheral muscarinic acetylcholine receptor blockade with intravenous atropine reduced ghrelin's gut motility effects
- c-Fos immunohistochemistry showed ghrelin upregulated neuronal activation in the PVN, other central nuclei, and enteric nervous plexuses of the stomach, duodenum, and proximal colon — all dependent on central GHSR activation
Wang, Yan; Chen, Fenrong; Shi, Haitao; Jiang, Jiong; Li, Hong; Qin, Bin; Li, Yong ·
RPEP-02835 · 2015The hunger hormone peptide ghrelin partially protected against cisplatin-induced testicular damage and cachexia (muscle wasting) in male mice. When given alongside cisplatin chemotherapy, ghrelin significantly increased body, testicular, and epididymal weights while reducing testicular cell death. The widespread damage to sperm-producing tissue (seminiferous epithelium) caused by cisplatin was less severe with ghrelin co-treatment. Critically, these protective effects were absent in mice lacking the ghrelin receptor (GHSR-1a), confirming the effects are specifically mediated through this receptor and not off-target.
Whirledge, Shannon D; Garcia, Jose M; Smith, Roy G; Lamb, Dolores J · Animal Study
RPEP-02849 · 2015Using the crystal structure of the BRC4-RAD51(191-220) complex, a series of BRC4 mutant peptides was designed with PyMOL and synthesized via Fmoc solid-phase methods to >95% purity. Circular dichroism spectroscopy revealed slight secondary structure changes in the mutant peptides, indicating that mutations at non-conserved sites in BRC4 can affect the interaction interface with RAD51. These structural changes provide insights into the binding rules governing BRCA2-RAD51 interaction.
Zhao, Dongxin; Lu, Kui ·
RPEP-02852 · 2015Both low (0.1 nM) and high (1.0 nM) concentrations of Substance P enhanced tendon-derived stem cell (TDSC) proliferation in vitro. However, low-dose SP induced tenocyte-related gene expression (promoting healthy tendon cell identity), while high-dose SP induced non-tenocyte genes including PPARγ (a fat cell marker) and collagen type II (a cartilage marker).
In vivo, injecting low-dose SP (0.5 nmol) into rat patella tendons enhanced tenogenesis compared to both saline controls and high-dose SP. High-dose SP (5.0 nmol) induced tendinosis-like changes in the tendon. These findings demonstrate a clear dose-dependent switch from therapeutic to pathological effects.
Zhou, Y; Zhou, B; Tang, K ·
RPEP-02859 · 2016Double-stranded RNA acting as a damage signal significantly increased expression of multiple growth factors in keratinocytes, endothelial cells, and fibroblasts. When LL-37 was added alongside dsRNA — mimicking real wound conditions — RNA sequencing revealed even greater growth factor upregulation.
Specifically, keratinocytes exposed to both LL-37 and dsRNA showed increased expression of FGF2 (basic fibroblast growth factor), HBEGF (heparin-binding EGF-like growth factor), VEGFC (vascular endothelial growth factor C), betacellulin, EGF, epiregulin, and members of the TGF-β superfamily. These results were validated by quantitative PCR and ELISA, confirming that antimicrobial peptides play a direct role in stimulating tissue repair — not just fighting infection.
Adase, Christopher A; Borkowski, Andrew W; Zhang, Ling-Juan; Williams, Michael R; Sato, Emi; Sanford, James A; Gallo, Richard L ·
RPEP-02861 · 2016None of the four proglucagon-derived peptides caused acute harm to the exocrine pancreas:
- Plasma amylase did not increase after infusion of GLP-1, oxyntomodulin, glucagon, or exendin-4 (compared to vehicle and cholecystokinin controls)
- None of the peptides caused significant cell proliferation in pancreatic acinar or ductal cells
- None increased amylase secretion from isolated pancreatic cells
- Oxyntomodulin specifically inhibited plasma amylase when co-administered with cholecystokinin, suggesting an active protective mechanism
This positions oxyntomodulin as potentially the safest proglucagon-derived peptide for obesity treatment regarding pancreatic risk.
Akalestou, Elina; Christakis, Ioannis; Solomou, Antonia M; Minnion, James S; Rutter, Guy A; Bloom, Stephen R ·