RPEP-02868 · 2016GHK-Cu (glycyl-histidyl-lysine copper) is surprisingly stable in water and at pH 4.5–7.4 buffers, remaining intact for at least two weeks even at 60°C. However, it breaks down under basic (alkaline) and oxidative conditions through hydrolytic cleavage, with histidine identified as one of three degradation products.
The peptide is highly water-loving (hydrophilic), with log D values between -2.38 and -2.49, which explains why it struggles to penetrate skin on its own. It was compatible with Span 60-based niosomes (a type of delivery vesicle) but degraded in the presence of negatively charged lipids like dicetyl phosphate. These findings provide a practical roadmap for formulating GHK-Cu into effective topical products.
Badenhorst, Travis; Svirskis, Darren; Wu, Zimei · Laboratory
RPEP-02871 · 2016The review describes a comprehensive model of gut-brain energy regulation:
- Enteroendocrine cells sense ingested nutrients and release gut peptides (CCK, GLP-1, PYY)
- These peptides signal via two pathways: paracrine signaling through vagal and non-vagal neuronal relays, and endocrine signaling via the bloodstream
- Central nervous system integrates these signals to generate responses that reduce food intake and increase energy expenditure
- Gut microbiota modulate this gut-brain axis, potentially influencing the development of obesity
- Disruptions in this signaling system may contribute to impaired energy homeostasis and weight gain
Bauer, Paige V; Hamr, Sophie C; Duca, Frank A ·
RPEP-02874 · 2016This study provided the first evidence that VIP receptors (VPAC1 and VPAC2) are expressed in the epithelium of healthy human hair follicles at both gene and protein levels. In lesional hair bulbs of alopecia areata patients, VIP receptor protein expression was significantly downregulated, while VIP-positive nerve fibers remained present — suggesting a defect in receptor-mediated signaling rather than peptide supply.
In hair follicle organ culture, VIP treatment protected follicles from interferon-γ-induced immune privilege collapse but did not fully restore immune privilege once it had already collapsed. This indicates VIP acts as a preventive 'guardian' of hair follicle immune privilege rather than a restorative agent.
Bertolini, M; Pretzlaff, M; Sulk, M; Bähr, M; Gherardini, J; Uchida, Y; Reibelt, M; Kinori, M; Rossi, A; Bíró, T; Paus, R ·
RPEP-02875 · 2016Kisspeptin (Kp) and RFRP neurons are positioned at a critical interface between the suprachiasmatic nucleus (SCN) — the brain's master circadian clock — and GnRH neurons, which control the hormonal cascade leading to ovulation. Kisspeptin stimulates GnRH release, while RFRP generally inhibits it, creating a push-pull system for precisely timing the preovulatory hormone surge.
The review also reports that these neuropeptide neurons are themselves part of the multi-oscillatory circadian system, meaning they don't just relay clock signals but actively participate in circadian timekeeping for reproduction. Recent investigations suggest potential therapeutic applications of these peptides in human reproductive disorders.
Beymer, Matthew; Henningsen, Jo; Bahougne, Thibault; Simonneaux, Valérie ·
RPEP-02877 · 2016Psoriatic skin showed broad, strong expression of all eight antimicrobial peptides tested, with particularly robust keratinocyte expression. In contrast, psoriatic arthritis synovial tissue only expressed S100 A8, S100 A9, and HNP1-3, and only in the synovium sublining layer — not in the lining layer.
Critically, hBD-2, hBD-3, psoriasin (S100 A7), RNase 7, and cathelicidin LL-37 were completely undetectable in the joint tissue of PsA, RA, or OA patients. Since hBD-2 is genetically linked to psoriasis susceptibility, its skin-only expression provides a molecular explanation for why psoriasis and psoriatic arthritis behave as distinct — though related — diseases.
Bierkarre, H; Harder, J; Cuthbert, R; Emery, P; Leuschner, I; Mrowietz, U; Hedderich, J; McGonagle, D; Gläser, R ·
RPEP-02878 · 2016Substance P (SP) mediates neurogenic inflammation in the eye through binding to the neurokinin-1 receptor (NK-1R), which is expressed on nerves, immune cells, and epithelial cells. SP's inflammatory effects include:
- Increased microvascular permeability and vasodilatation
- Plasma extravasation and tissue edema
- Stimulation of macrophages to release interleukins, chemokines, and growth factors
Inhibition of SP activity — through blocking neuropeptide release or using NK-1R antagonists — ameliorates ocular inflammation, restores immune privilege, and improves clinical endpoints including corneal opacity, ocular perforation, and angiogenesis. These effects have been demonstrated in animal models and in human eye diseases.
Bignami, Fabio; Rama, Paolo; Ferrari, Giulio ·
RPEP-02881 · 2016The review highlights the complex structure-function relationships of amylin and its receptors, emphasizing the challenges posed by amylin's aggregation and solubility issues. Insights from related peptides like CGRP are used to inform the design of more potent and stable amylin mimetics, including peptide hybrids.
Bower, Rebekah L; Hay, Debbie L ·
RPEP-02882 · 2016KL4 (sinapultide) is the first synthetic peptide designed to replace surfactant protein B in lung surfactant therapies. Its formulation, Surfaxin, demonstrated that synthetic peptide-based surfactants can replace animal-derived surfactants for treating respiratory distress syndromes and acute lung injury. Structural studies revealed KL4 has adaptive helical properties — its shape changes depending on lipid environment and pH — with a five-amino-acid repeat pattern that enables it to interact differently with various lipid layers.
This structural plasticity appears to be key to how KL4 helps form stable DPPC monolayers at the air-water interface in the lungs — the same function that natural surfactant protein B performs to keep lung air sacs from collapsing.
Braide-Moncoeur, Otonye; Tran, Nhi T; Long, Joanna R · Review
RPEP-02889 · 2016Opioid receptors on immune cells (leukocytes) can trigger the release of three opioid peptides — Met-enkephalin, β-endorphin, and dynorphin A (1-17) — which then act on nearby nerve cell receptors to relieve neuropathic pain. This challenges the classical view that opioid pain relief works only through receptors on neurons.
The researchers mapped the complete signaling pathway: activation of leukocyte opioid receptors triggers a Gαi/o-Gβγ protein cascade through phospholipase C and IP3 receptors, releasing intracellular calcium, which drives opioid peptide secretion. When leukocytes were depleted, pain relief from exogenous opioids was significantly reduced and could only be restored by transplanting wild-type immune cells — not those lacking opioid receptors.
Celik, Melih Ö; Labuz, Dominika; Henning, Karen; Busch-Dienstfertig, Melanie; Gaveriaux-Ruff, Claire; Kieffer, Brigitte L; Zimmer, Andreas; Machelska, Halina ·
RPEP-02890 · 2016GHRP-2 (a synthetic ghrelin analog) suppressed inflammation in human ovarian granulosa cells through multiple mechanisms. It reduced the expression and secretion of two key inflammatory mediators — COX-2 and IL-8 — by blocking the p38, JNK, and NF-κB signaling pathways that drive their production.
Beyond blocking production, GHRP-2 also accelerated the breakdown of already-existing COX-2 and IL-8 proteins by activating both proteasomal and lysosomal degradation pathways. The anti-inflammatory effect depended on two phosphatases (MKP-1 and PP2A), suggesting GHRP-2 works by activating the cell's own inflammation-shutoff switches.
Chao, Yi-Ning; Sun, David; Peng, Yen-Chun; Wu, Yuh-Lin · In Vitro
RPEP-02894 · 2016Both SP and NK1R were significantly upregulated in CRC tissue compared to adjacent normal tissue (P<0.001). High SP expression was significantly associated with lymph node metastasis (P<0.001). High NK1R expression was significantly related to TNM stage (P=0.010) and lymph node metastasis (P=0.019).
SP and NK1R expression were highly correlated with each other (r=0.419, P<0.001), suggesting coordinated upregulation of the signaling pathway in tumors.
Survival analysis showed significantly poorer prognosis for patients with high SP or NK1R expression (P<0.05). Multivariate Cox regression confirmed that SP expression was independently correlated with survival, alongside lymph node metastasis and distant metastasis — meaning SP levels predict outcomes even after accounting for other known prognostic factors.
Chen, Xiao-Yi; Ru, Guo-Qing; Ma, Ying-Yu; Xie, Jun; Chen, Wan-Yuan; Wang, Hui-Ju; Wang, Shi-Bing; Li, Li; Jin, Ke-Tao; He, Xiang-Lei; Mou, Xiao-Zhou ·
RPEP-02895 · 2016Two peptides were identified from trypsin-digested Nile tilapia skin gelatin: GPEGPAGAR (810.87 Da) and GETGPAGPAGAAGPAGPR (1490.61 Da). The trypsin B fraction showed ACE inhibitory activity of 59.32 ± 9.97% and radical scavenging activity of 8.16 ± 2.18 µg trolox/mg peptide. The trypsin A fraction had the greatest reducing power at 5.138 ± 1.060 µM trolox/mg peptide.
Molecular docking analysis suggested the shorter peptide may fit slightly better into the ACE binding cleft, but both synthetic peptides showed no significant difference in ACE inhibitory activity in vitro, confirming their dual potential as antioxidant and antihypertensive agents.
Choonpicharn, Sadabpong; Tateing, Suriya; Jaturasitha, Sanchai; Rakariyatham, Nuansri; Suree, Nuttee; Niamsup, Hataichanoke ·
RPEP-02896 · 2016The GHRH receptor (GHRH-R) was found to be highly expressed in retinoblastoma cells but not in other retinal cells, providing a selective target. Two GHRH-R antagonists, MIA-602 and MIA-690, induced specific apoptosis in retinoblastoma cells without triggering cell death in retinal pigmented epithelial cells.
Gene expression profiling revealed that GHRH-R antagonists downregulated cell proliferation genes while upregulating apoptotic genes in the cancer cells. The mechanism exploits the fact that retinoblastoma arises from cone precursor cells with high MDM2 levels that suppress p53-mediated apoptosis — the GHRH-R antagonists appear to restore these suppressed cell death pathways.
Chu, Wai Kit; Law, Ka Sin; Chan, Sun On; Yam, Jason Cheuk Sing; Chen, Li Jia; Zhang, Hao; Cheung, Herman S; Block, Norman L; Schally, Andrew V; Pang, Chi Pui ·
RPEP-02902 · 2016Substance P expression increases after acute CNS injury, with the magnitude of release correlating to both the frequency and severity of the insult. SP release directly promotes blood-brain barrier permeability, vasogenic edema formation, neuronal injury, and worse functional outcomes.
NK1 receptor antagonists that block Substance P's actions showed high therapeutic benefit in both focal and diffuse models of traumatic brain injury, as well as in ischemic stroke models. The therapeutic window extends up to 12 hours post-injury, making this a potentially practical intervention for emergency medicine settings.
Corrigan, F; Vink, R; Turner, R J ·
RPEP-02903 · 2016TRP channels (TRPV1 and TRPA1) are activated by mechanical forces during brain injury, causing the release of substance P. This neuropeptide then drives multiple inflammatory processes: activating microglia and astrocytes, degranulating mast cells, promoting immune cell migration into the brain, and critically, increasing blood-brain barrier permeability through caveolae-mediated transcellular transport. This neurogenic inflammation creates a positive feedback loop with classical inflammation — bradykinin and prostaglandins from classical pathways further stimulate TRP channels, perpetuating neuropeptide release and escalating damage.
Corrigan, Frances; Mander, Kimberley A; Leonard, Anna V; Vink, Robert ·
RPEP-02907 · 2016A young female patient with sporadic X-LAG syndrome showed consistently elevated circulating GHRH levels accompanied by marked GH and prolactin hypersecretion. In vitro, the GHRH receptor antagonist acetyl-(d-Arg2)-GHRH(1-29) amide blocked GHRH-induced GH stimulation and, importantly, also significantly reduced baseline GH release when used alone.
Pasireotide (a somatostatin analog) inhibited GH secretion, but octreotide did not. A ghrelin receptor agonist and inverse agonist produced modest but statistically significant changes in GH secretion. These data suggest hypothalamic GHRH dysregulation is part of X-LAG syndrome pathology and that GHRH blockade could be a therapeutic strategy.
Daly, Adrian F; Lysy, Philippe A; Desfilles, Céline; Rostomyan, Liliya; Mohamed, Amira; Caberg, Jean-Hubert; Raverot, Veronique; Castermans, Emilie; Marbaix, Etienne; Maiter, Dominique; Brunelle, Chloe; Trivellin, Giampaolo; Stratakis, Constantine A; Bours, Vincent; Raftopoulos, Christian; Beauloye, Veronique; Barlier, Anne; Beckers, Albert ·
RPEP-02911 · 2016A duodenal-jejunal bypass liner (DJBL) — a non-surgical sleeve placed in the upper intestine — produced 12.7 kg weight loss over 24 weeks while significantly altering appetite-regulating peptide hormones. Postprandial PYY increased from 2.6 to 4.1 nmol/L/min (p<0.05) and ghrelin from 7.8 to 11.0 ng/mL/min (p<0.05) within the first week. CCK response decreased from 434 to 229 pmol/L/min (p<0.01). Fasting leptin dropped from 98 to 53 ng/mL (p<0.01). These hormonal changes occurred rapidly (within 1 week) and persisted through 24 weeks.
de Jonge, Charlotte; Rensen, Sander S; Verdam, Froukje J; Vincent, Royce P; Bloom, Steve R; Buurman, Wim A; le Roux, Carel W; Bouvy, Nicole D; Greve, Jan Willem M ·
RPEP-02912 · 2016The primary endpoint was not met: HbA1c change did not significantly differ between groups (-0.5% with liraglutide vs -0.3% with placebo; between-group difference -0.2%, p=0.18). However, several clinically meaningful secondary benefits emerged:
- Body weight: -6.8 kg difference favoring liraglutide (p=0.015)
- Bolus insulin: -5.8 IU difference (p=0.023)
- Hypoglycemic events: 18% reduction (incident rate ratio 0.82, p<0.001)
- Heart rate: +7.5 bpm increase with liraglutide (p=0.002)
- Gastrointestinal side effects: nausea 58% vs 10%, dyspepsia 22% vs 2%
Gastric emptying was initially delayed at 3 weeks but normalized by 24 weeks.
Dejgaard, Thomas Fremming; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk; Almdal, Thomas; Urhammer, Søren; Pedersen-Bjergaard, Ulrik; Jensen, Tonny; Jensen, Andreas Kryger; Holst, Jens Juul; Tarnow, Lise; Knop, Filip Krag; Madsbad, Sten; Andersen, Henrik Ullits ·
RPEP-02913 · 2016In 20 patients with secondary headaches and nasal contact points, surgery produced significant headache reduction measured by visual analog scale at 3 months (p<0.001) and 12 months (p<0.001) postoperatively.
However, fluorescein staining for substance P (p=0.631), neurokinin A (p=0.546), and CGRP (p=0.683) showed no statistically significant differences between contact mucosa and non-contact mucosa. This dissociation between clinical improvement and neuropeptide levels suggests the mechanism of headache relief from surgery involves factors other than local neuropeptide accumulation.
Demir, Deniz; Cengiz, Nureddin; Güven, Mehmet; Bulduk, Oğuzhan ·
RPEP-02915 · 2016Doxycycline 40-mg modified-release capsules significantly reduced inflammatory lesions and improved investigator global assessment scores compared to placebo over 12 weeks. Cathelicidin expression and protein levels decreased during treatment. Low levels of protease activity and cathelicidin expression at 12 weeks correlated with treatment success. Low baseline protease activity predicted clinical response to doxycycline, suggesting it could serve as a predictive biomarker for treatment selection.
Di Nardo, Anna; Holmes, Anna D; Muto, Yumiko; Huang, Eugene Y; Preston, Norman; Winkelman, Warren J; Gallo, Richard L ·
RPEP-02916 · 2016Children with allergic rhinitis had significantly lower nasal fluid LL-37 levels than healthy controls (median 2.3 ng/ml vs. 2.6 ng/ml, p<0.001). The levels were further reduced in moderate/severe AR compared to mild AR (2.2 ng/ml vs. 2.5 ng/ml, p<0.001). All AR patients were newly diagnosed and medication-free, eliminating treatment as a confounding factor.
Dilek, F; Gultepe, B; Ozkaya, E; Yazici, M; Gedik, A H; Cakir, E ·
RPEP-02922 · 2016A library of stabilized α-helices of OLIG2 (SAH-OLIG2) was developed using hydrocarbon stapling of varying lengths and sequences. Key findings:
• Stapling successfully reinforced the α-helical structure of all bHLH constructs tested
• Despite structural stabilization, sequence-specific dissociation of OLIG2 dimers from DNA was not achieved
• Re-evaluation of binding determinants revealed an unanticipated role of the C-terminal domain in OLIG2 self-association and stability
• The positively charged amino acid sequences inherent to bHLH domains created liabilities for peptide-based targeting
• The multifactorial binding determinants of OLIG2 (not just the helix-loop-helix region) complicate the decoy peptide approach
Edwards, Amanda L; Meijer, Dimphna H; Guerra, Rachel M; Molenaar, Remco J; Alberta, John A; Bernal, Federico; Bird, Gregory H; Stiles, Charles D; Walensky, Loren D ·
RPEP-02930 · 2016This review establishes LL-37 as far more than an antimicrobial peptide. As the sole human cathelicidin, LL-37 serves as a broad-spectrum natural antibiotic, but also has potent chemotactic properties (attracting immune cells to sites of infection) and immunomodulatory effects. The authors analyzed LL-37’s therapeutic potential across four major systems: immune, respiratory, gastrointestinal, and skin — identifying specific molecular pathways and disease connections in each.
Fabisiak, Adam; Murawska, Natalia; Fichna, Jakub · Review
RPEP-02931 · 2016D-amino acid incorporation into peptides provides resistance to enzymatic degradation, significantly extending their biostability. The review covers three key applications: (1) traditional use of D-amino acid substitution to make peptide drugs last longer in the body, (2) mirror-image phage display and retro-inverso synthesis to discover all-D-amino acid peptide therapeutics, and (3) an emerging application — enzyme-instructed self-assembly (EISA) — where D-amino acid peptides selectively form nanostructures inside specific cells (cancer cells or inflammatory cells) to kill them.
Feng, Zhaoqianqi; Xu, Bing ·
RPEP-02937 · 2016GHRH receptors are expressed on pancreatic beta-cells, and GHRH agonists can directly stimulate insulin secretion through signaling pathways similar to those used in the pituitary gland. Engineered GHRH analogs have been shown to:
- Increase insulin secretion from isolated pancreatic islets
- Preserve beta-cell function and survival
- Potentially improve glucose metabolism in type 2 diabetes
- Provide additional benefits including wound healing and cardioprotection
The review proposes that GHRH agonists could serve a dual role: improving insulin secretion while also protecting against diabetic complications like poor wound healing and cardiovascular damage.
Fridlyand, Leonid E; Tamarina, Natalia A; Schally, Andrew V; Philipson, Louis H ·
RPEP-02939 · 2016Survival analysis across multiple cohorts of gastric cancer patients established that increased GHRH receptor expression in tumor tissue independently predicts poor survival. The GHRH receptor antagonist MIA-602 effectively inhibited gastric cancer cell growth in vitro across multiple human cell lines.
These results were confirmed in vivo using xenograft mouse models with human gastric cancer cells. Mechanistically, MIA-602 targets the GHRH receptor and downregulates the PAK1-mediated STAT3/NF-κB inflammatory pathway, providing a clear molecular explanation for its anticancer effects.
Gan, Jinfeng; Ke, Xiurong; Jiang, Jiali; Dong, Hongmei; Yao, Zhimeng; Lin, Yusheng; Lin, Wan; Wu, Xiao; Yan, Shumei; Zhuang, Yixuan; Chu, Wai Kit; Cai, Renzhi; Zhang, Xianyang; Cheung, Herman S; Block, Norman L; Pang, Chi Pui; Schally, Andrew V; Zhang, Hao ·
RPEP-02947 · 2016GLP-1 receptor agonists appear to modestly lower systolic blood pressure by approximately 2 mmHg with chronic use, but the effect is inconsistent. A single dose can actually increase blood pressure acutely. Two controlled clinical trials that measured ambulatory blood pressure as the primary endpoint did not consistently confirm the blood pressure–lowering effect.
GLP-1 drugs also increase heart rate. The blood pressure reduction observed in diabetes trials may partly reflect weight loss rather than a direct drug effect. Animal studies suggest the drugs could act through vascular, kidney, heart, and brain pathways, but these mechanisms haven't been confirmed in humans.
Goud, Aditya; Zhong, Jixin; Peters, Matthew; Brook, Robert D; Rajagopalan, Sanjay · Review
RPEP-02948 · 2016Activity-dependent neuroprotective protein (ADNP) is essential for brain formation and function, and mutations in the ADNP gene are a leading cause of autism. The ADNP protein interacts with the cell's cytoskeleton through microtubule end-binding (EB) proteins and with the autophagy regulator LC3.
Critically, the peptide drug candidate NAP (davunetide, sequence NAPVSIPQ) — derived from ADNP — shares the same SIP domain that mediates ADNP's binding to EB proteins. This identifies a precise molecular target for NAP/davunetide's neuroprotective effects: it protects brain cells by stabilizing the cytoskeleton through the same binding site that ADNP naturally uses. ADNP was also found to be part of the SWI/SNF chromatin remodeling complex, linking it to tau splicing and tauopathy prediction.
Gozes, Illana · Review / Perspective
RPEP-02950 · 2016The rice bran-derived pentapeptide inhibited human prostate cancer cell growth by 45% at 460 μg/mL. When incorporated into spray-dried orange juice, the peptide showed approximately 10% degradation at 620 μg/mL under refrigerated storage over six months, with higher degradation at ambient temperature and lower concentrations. Sensory evaluation indicated good acceptability except for a slight bitterness.
Graves, Amanda M; Hettiarachchy, Navam; Rayaprolu, Srinivas; Li, Ruiqi; Horax, Ronny; Seo, Han-Seok ·
RPEP-02955 · 2016Short-acting and long-acting GLP-1 receptor agonists work through different primary mechanisms despite sharing the same target. Short-acting agents (like twice-daily exenatide) primarily reduce postprandial glucose spikes by slowing gastric emptying, while long-acting agents (like once-weekly exenatide) mainly lower fasting blood glucose by sustained stimulation of pancreatic insulin secretion.
Only about half of type 2 diabetes patients on standard drugs achieve adequate glycemic control (HbA1c <7%), largely due to poor adherence. Exenatide as add-on therapy showed consistent benefits across a large evidence base, with good tolerability and no new safety signals during up to 5 years of follow-up. The clinical differences between formulations allow individualized treatment based on whether a patient's main problem is postmeal spikes or high fasting glucose.
Guo, Xiao-Hui · Review
RPEP-02956 · 2016Self-assembled peptide nanostructures offer several key advantages as drug delivery vehicles: chemical diversity that allows customization, biocompatibility with human tissue, high loading capacity for both hydrophobic and hydrophilic drugs, and the ability to target specific molecular recognition sites on cells.
By incorporating novel peptide motifs, researchers can make these structures stimuli-responsive — meaning they remain stable during transport through the body but release their drug cargo when they encounter specific conditions (like the acidic environment of a tumor or certain enzymes at an infection site).
Habibi, Neda; Kamaly, Nazila; Memic, Adnan; Shafiee, Hadi ·
RPEP-02958 · 2016The novel dual GLP-1/GIP receptor agonist significantly reduced neurological deficits, infarct volume, apoptotic neuron percentage, and inflammation markers compared to a GLP-1 receptor agonist alone, indicating superior neuroprotection in a rat model of transient focal cerebral ischemia.
Han, Ling; Hölscher, Christian; Xue, Guo-Fang; Li, Guanglai; Li, Dongfang ·
RPEP-02960 · 2016Abaloparatide (a synthetic analog of PTHrP) binds more selectively to the RG conformation of the PTH type 1 receptor (PTHR1) compared to the R0 conformation, while PTH(1-34) (teriparatide) binds both conformations more equally.
This RG-selective binding produces more transient cAMP signaling responses in PTHR1-expressing cells. Because transient (intermittent-like) receptor activation favors bone formation over bone resorption, this receptor selectivity provides a molecular explanation for why abaloparatide may build bone with less accompanying bone loss and fewer hypercalcemic side effects than teriparatide.
Hattersley, Gary; Dean, Thomas; Corbin, Braden A; Bahar, Hila; Gardella, Thomas J · In Vitro / Mechanistic
RPEP-02963 · 2016Using E. coli proteome microarrays, the researchers mapped intracellular targets for four AMPs:
- Bactenecin 7 (Bac7): targets purine metabolism and histidine kinase
- Lactoferricin B (LfcinB): attacks transcription-related activities and carbohydrate biosynthesis
- Pleurocidin-dermaseptin hybrid (P-Der): affects small molecule catabolic processes
- Proline-arginine-rich peptide (PR-39): recognizes RNA and folate metabolism proteins
Overlapping targets revealed synergistic potential: Bac7 and LfcinB both target purine metabolism, while LfcinB and PR-39 both target lipopolysaccharide biosynthesis. These predicted synergies were confirmed in antimicrobial assays.
All four AMPs target arginine decarboxylase, essential for E. coli survival in extremely acidic environments. Correspondingly, all four showed greater bacterial growth inhibition under acidic conditions, confirmed experimentally.
Ho, Yu-Hsuan; Shah, Pramod; Chen, Yi-Wen; Chen, Chien-Sheng ·
RPEP-02965 · 2016Through computational modeling and amino acid replacement experiments, the study revealed that the first three residues of the peptidomimetic G-7039 bind to three distinct hydrophobic sub-pockets in the ghrelin receptor (GHS-R1a). Contrary to previous reports suggesting that a charge-charge interaction between the agonist's terminal amine and Glu124 serves as the primary anchor point, this study demonstrated that this electrostatic interaction alone is insufficient to anchor the ligand — hydrophobic interactions are the dominant binding force.
Hou, Jinqiang; Charron, Carlie L; Fowkes, Milan M; Luyt, Leonard G ·
RPEP-02973 · 2016Collagen hydrolysates (broken-down collagen peptides) improved blood sugar control in mice through two distinct mechanisms: they inhibited glucose absorption in the intestine (partially through GLP-1) and they enhanced insulin secretion (independent of GLP-1). The collagen peptides also inhibited DPP-IV enzyme activity and stimulated GLP-1 secretion in lab tests. Blocking the GLP-1 receptor only partially reversed the glucose-lowering effect and actually enhanced the insulin secretion boost, confirming that collagen peptides work through multiple pathways.
Iba, Yoshinori; Yokoi, Koji; Eitoku, Itsuka; Goto, Masaki; Koizumi, Seiko; Sugihara, Fumihito; Oyama, Hiroshi; Yoshimoto, Tadashi ·
RPEP-02975 · 2016The high-content collagen peptide supplement (H-CP) significantly improved all four measured skin parameters compared to placebo at 8 weeks: facial skin moisture, elasticity (R2 measurement), wrinkle depth, and skin roughness. It also outperformed the low-content collagen peptide supplement (L-CP), establishing a dose-response relationship based on Pro-Hyp and Hyp-Gly content.
The mechanism is supported by prior evidence showing that Pro-Hyp and Hyp-Gly appear in peripheral blood after collagen ingestion, attract dermal fibroblasts (the cells that maintain skin structure), enhance their proliferation, and stimulate hyaluronic acid production — a key molecule for skin hydration. Safety evaluation via blood tests showed no adverse events during the trial.
Inoue, Naoki; Sugihara, Fumihito; Wang, Xuemin ·
RPEP-02980 · 2016Resolvin E1 (RvE1), a molecule derived from omega-3 fatty acids, blocked the ability of substance P — a key pain-signaling neuropeptide — to amplify TRPV1 pain receptor activity in mouse sensory neurons. Even at low concentrations, RvE1 strongly inhibited this pain-sensitizing pathway.
The mechanism works through a specific receptor called ChemR23 on pain-sensing neurons. When RvE1 activates ChemR23, it triggers a G-protein signaling cascade that counteracts substance P's ability to sensitize TRPV1. Researchers confirmed this by showing that blocking G-protein signaling (with pertussis toxin and GDPβ-S) eliminated RvE1's inhibitory effect. This positions RvE1 as a natural anti-inflammatory pain inhibitor that directly opposes substance P-driven pain sensitization.
Jo, Youn Yi; Lee, Ji Yeon; Park, Chul-Kyu · Basic Research
RPEP-02988 · 2016Pyrosequencing revealed allelic imbalance of oxytocin receptor (Oxtr) mRNA, demonstrating that genetic variants directly influence receptor expression — but only in specific brain regions, including the nucleus accumbens, where oxytocin signaling facilitates pair bonding. Next-generation sequencing identified a single polymorphism in an Oxtr intron, near a putative cis-regulatory element, that explained 74% of the variance in striatal Oxtr expression.
The behavioral consequence was striking: male prairie voles homozygous for the high-expressing allele displayed significantly enhanced social attachment in the partner preference test — the gold-standard behavioral assay for pair bonding in this species. The brain region-specificity of the genetic effect is notable: the same variant influenced expression in the nucleus accumbens but not in other oxytocin receptor-rich brain regions.
King, Lanikea B; Walum, Hasse; Inoue, Kiyoshi; Eyrich, Nicholas W; Young, Larry J ·
RPEP-02990 · 2016GHRH agonists JI-34 and MR-356 significantly improved viability of irradiated neonatal rat cardiac myocytes and reduced radiation-induced reactive oxygen species (ROS) levels. JI-34 showed protective effects at 10 and 100 nM concentrations, while MR-356 was protective at 500 nM. JI-34 also interfered with the activation of SAFE/RISK signaling pathways. Notably, neither compound affected cell viability or proliferation in unirradiated cells, suggesting a radiation-specific protective mechanism.
Kiscsatári, Laura; Varga, Zoltán; Schally, Andrew V; Gáspár, Renáta; Nagy, Csilla Terézia; Giricz, Zoltán; Ferdinandy, Péter; Fábián, Gabriella; Kahán, Zsuzsanna; Görbe, Anikó ·
RPEP-02991 · 2016Neither bullfrog ghrelin nor rat ghrelin affected longitudinal smooth muscle contractility of gastrointestinal strips from bullfrogs or Japanese fire belly newts. The ghrelin receptor (GHS-R1a) mRNA was confirmed present in the bullfrog GI tract, with higher expression in intestinal mucosa than gastric mucosa — yet the receptor did not mediate contractile responses.
Other gastrointestinal peptides including substance P, neurotensin, and motilin, plus the muscarinic agonist carbachol, all induced marked contractions, confirming the muscle preparations were functional. This was the first demonstration that motilin induces gastrointestinal contraction in amphibians. The results parallel findings in fish (rainbow trout, goldfish) where ghrelin also lacks gut motility effects, but contrast with mammals and birds where ghrelin is a potent gut motility regulator.
Kitazawa, Takio; Shimazaki, Misato; Kikuta, Ayumi; Yaosaka, Noriko; Teraoka, Hiroki; Kaiya, Hiroyuki ·
RPEP-02995 · 2016BPC 157 administered locally (eye drops, 0.4 µg/eye) or systemically (intraperitoneal, 10 µg, 10 ng, or 10 pg/kg) had no effect on normal pupil size in either rats or guinea pigs. However, BPC 157 alone consistently counteracted atropine-induced mydriasis (pupil dilation) in both species and both routes of administration.
In its interactions with NO modulators, BPC 157 prolonged L-arginine-induced miosis (pupil constriction) and shortened L-NAME-induced miosis, demonstrating differential effects on the two arms of the NO system. When combined with L-NAME and/or L-arginine in atropine-dilated pupils, BPC 157 generally augmented their ability to counteract mydriasis. L-NAME and L-arginine independently produced miosis in normal pupils that was NO-specific (they attenuated each other when combined).
Kokot, Antonio; Zlatar, Mirna; Stupnisek, Mirjana; Drmic, Domagoj; Radic, Radivoje; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag ·
RPEP-02998 · 2016Orthodontic tooth movement activates peripheral sensory nerve endings in the periodontium, which transmit pain signals to the trigeminal spinal nucleus, triggering c-Fos gene expression and concurrent inflammation involving astrocytes, microglia, and neurons.
Activated periodontal sensory fibers release the neuropeptides Substance P and CGRP locally, which induce an inflammatory cascade that is essential for alveolar bone turnover and tooth movement. NSAIDs and other painkillers effectively reduce pain but also suppress this neurogenic inflammatory component, slowing bone turnover and consequently delaying orthodontic treatment progression.
Kyrkanides, Stephanos; Huang, Hechang; Faber, Richard D ·
RPEP-02999 · 2016In a chronic constriction injury model of neuropathic pain, exogenous opioid agonists (including peptidergic ligands) effectively reduced heat hypersensitivity when applied perineurally. However, endogenous opioid peptides β-endorphin, Met-enkephalin, and dynorphin A did not alleviate heat hypersensitivity — even when their release was triggered by corticotropin-releasing factor applied perineurally.
Critically, exogenous opioids were equally effective in wild-type and opioid peptide-knockout mice, proving that endogenous opioids do not contribute to exogenous opioid analgesia in heat pain. Even when opioid peptides were applied exogenously (administered as drugs rather than released from immune cells), they were ineffective against heat pain. Conversely, endogenous opioid peptides did successfully relieve mechanical hypersensitivity, establishing a clear modality-specific distinction.
Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina ·
RPEP-03006 · 2016A topical complex of 5-aminolevulinic acid (5-ALA) and GHK peptide (ALAVAX) significantly increased hair count in men with pattern hair loss over 6 months compared to placebo. The 50 mg/ml group showed the strongest results, with a mean increase of 71.5 hairs (p<0.05) versus only 9.6 hairs in the placebo group. The ratio of change in hair count between the 50 mg/ml group (2.38) and placebo (1.21) was statistically significant (p<0.05).
Interestingly, the higher-dose 100 mg/ml group showed a hair count increase of 52.6, which was also significant versus baseline but numerically lower than the 50 mg/ml group. Patient satisfaction was highest in the 100 mg/ml group (26.7% reporting good or better), though hair length and thickness did not significantly differ among groups. No adverse events were reported in any group.
Lee, Weon Ju; Sim, Hyun Bo; Jang, Yong Hyun; Lee, Seok-Jong; Kim, Do Won; Yim, Soon-Ho · Randomized Controlled Trial
RPEP-03009 · 2016The study identified that NPY projections to the basolateral amygdala originate mainly from the amygdalostriatal transition area and bed nucleus of the stria terminalis, with a distinct subpopulation coexpressing somatostatin. Conditioned fear increased NPY gene expression specifically in the amygdalostriatal transition area, indicating its role in fear regulation.
Leitermann, Randy J; Rostkowski, Amanda B; Urban, Janice H ·
RPEP-03013 · 2016This is the first systematic review dedicated to how incorporating D-amino acids (mirror-image building blocks) improves host defense peptides (HDPs). D-amino acid substitution consistently enhances HDPs by increasing resistance to enzymatic degradation, improving antimicrobial potency, and maintaining or broadening activity against bacteria and tumors. The review systematically catalogs the effects of D-AA incorporation across different HDP families, filling a gap in the literature where this strategy was frequently mentioned but never comprehensively analyzed.
Li, Hao; Anuwongcharoen, Nuttapat; Malik, Aijaz Ahmad; Prachayasittikul, Virapong; Wikberg, Jarl E S; Nantasenamat, Chanin · Review
RPEP-03014 · 2016After nearly 30 years of mystery, researchers identified NTCP (sodium taurocholate co-transporting polypeptide) as the liver-specific receptor that hepatitis B and hepatitis D viruses use to enter liver cells. This discovery opened four major research directions:
1. NTCP-expressing cell lines now allow researchers to study the full HBV replication cycle from its natural template (cccDNA) in the lab.
2. These cell systems enable high-throughput drug screening to find new anti-HBV treatments.
3. Animals engineered to express human NTCP provide new in vivo models for studying these uniquely human infections.
4. The peptide entry inhibitor Myrcludex B (bulevirtide) proved that blocking NTCP can prevent viral entry — a clinical proof-of-concept for this therapeutic approach.
Li, Wenhui; Urban, Stephan · Review
RPEP-03015 · 2016Protease-resistant GLP-1 mimetics including lixisenatide, liraglutide, and exenatide have demonstrated neuroprotective effects in preclinical models of neurodegenerative disease and shown first positive results in clinical trials for both Alzheimer's disease and Parkinson's disease patients.
Beyond single-target GLP-1 agonists, the review identified promising preclinical evidence for GIP agonists, DPP-IV inhibitors, oxyntomodulin, dual GLP-1/GIP agonists, and triple GLP-1/GIP/glucagon receptor agonists in neurodegenerative disease models. The shared mechanism of insulin dysregulation between diabetes and neurodegeneration provides a biological rationale for this therapeutic approach.
Li, Yanwei; Li, Lin; Hölscher, Christian ·
RPEP-03016 · 2016Metrnl is predominantly expressed in intestinal epithelial cells in both humans and mice, and it is mainly released into the gut lumen rather than the bloodstream. When researchers knocked out Metrnl specifically in intestinal epithelial cells, gut fluid Metrnl levels dropped significantly while serum levels were only marginally affected. The knockout mice showed decreased expression of key antimicrobial peptides Reg3g and lactotransferrin, but no changes in body weight, food intake, blood glucose, colon length, intestinal permeability, or mucus content under normal conditions.
Li, Zhi-Yong; Fan, Mao-Bing; Zhang, Sai-Long; Qu, Yi; Zheng, Si-Li; Song, Jie; Miao, Chao-Yu ·