RPEP-01891 · 2011Vildagliptin inhibited DPP-4 enzymatic activity by approximately 70% and increased active GLP-1 levels roughly 3-fold in plasma (p < 0.05 vs. untreated groups). However, ejection fraction remained equally depressed in all three MI groups compared to sham controls, regardless of whether vildagliptin was started immediately or three weeks after the heart attack.
Stress biomarkers ANP and BNP mRNA were elevated in all MI groups with no significant reduction from vildagliptin treatment. The drug also had no effect on cardiomyocyte size, capillary density, glucose levels, or body weight.
Yin, Meimei; Silljé, Herman H W; Meissner, Maxi; van Gilst, Wiek H; de Boer, Rudolf A ·
RPEP-01893 · 2011Engineered LF11 variants with enhanced hydrophobicity (via bulky amino acid addition or N-acylation) showed improved antimicrobial activity against E. coli that correlated with their ability to perturb bacterial membrane mimics.
Non-acylated and N-acylated peptides worked through distinct mechanisms: non-acylated peptides induced segregation of peptide-rich and peptide-poor lipid domains, while N-acylated peptides formed small heterogeneous domains with greater packing defects. N-acylated peptides also perturbed neutral lipid packing and increased membrane permeability, but their elevated binding to lipopolysaccharides partially counteracted this advantage. Both types increased membrane curvature stress. Transmission electron microscopy showed N-acylated peptides induced tubular outer membrane protrusions, and viability tests confirmed bacteria died before visible cell lysis.
Zweytick, Dagmar; Deutsch, Günter; Andrä, Jörg; Blondelle, Sylvie E; Vollmer, Ekkehard; Jerala, Roman; Lohner, Karl ·
RPEP-01895 · 2012The antiviral activity of bovine lactoferrin against influenza is entirely attributable to its C-lobe, which binds specifically to the HA2 region of viral hemagglutinin — the highly conserved domain containing the fusion peptide. All major virus subtypes tested (including H1N1 and H3N2) were inhibited.
Through molecular docking studies, three C-lobe peptide fragments were identified that inhibited both virus hemagglutination and cell infection at femtomolar concentrations — an extremely potent level of activity. The target (the fusion peptide region) is conserved across influenza subtypes, explaining the broad-spectrum activity.
Ammendolia, Maria Grazia; Agamennone, Mariangela; Pietrantoni, Agostina; Lannutti, Fabio; Siciliano, Rosa Anna; De Giulio, Beatrice; Amici, Carla; Superti, Fabiana ·
RPEP-01900 · 2012Twenty weeks of daily GHRH (tesamorelin) injections improved cognitive function in both healthy older adults and those with mild cognitive impairment. The effect was statistically significant in the intent-to-treat analysis (P=.03) and even stronger among those who completed the full protocol (P=.002).
The cognitive benefit was most pronounced for executive function (P=.005), which includes skills like planning, mental flexibility, and multitasking. There was also a trend toward improvement in verbal memory (P=.08). The treatment boosted IGF-1 levels by 117% while keeping them within the normal physiological range, and reduced body fat by 7.4%. In adults with MCI, fasting insulin rose by 35% but remained within normal limits. Adverse events were mild, reported by 68% of those on GHRH versus 36% on placebo.
Baker, Laura D; Barsness, Suzanne M; Borson, Soo; Merriam, George R; Friedman, Seth D; Craft, Suzanne; Vitiello, Michael V · Randomized Controlled Trial
RPEP-01902 · 2012Detecting peptide hormone doping in athletes remains one of the hardest challenges in anti-doping science. Unlike small-molecule drugs that leave clear metabolic traces, peptide hormones like growth hormone, EPO, and insulin-like growth factor are nearly identical to substances the body produces naturally. The review describes advances in mass spectrometry-based detection methods and immunological assays for WADA-prohibited peptides, while noting that many peptide hormones still can't be reliably detected.
The most promising future direction is the development of 'biomarker' approaches — instead of trying to detect the peptide itself, scientists look for downstream biological changes that betray its use. This indirect detection strategy may be the key to catching peptide doping.
Barroso, Osquel; Handelsman, David J; Strasburger, Christian; Thevis, Mario · Review
RPEP-01907 · 2012This historical review traces the 26-year journey from the first synthetic growth hormone-releasing peptides (GHRPs) in 1976 to the isolation of ghrelin from the stomach in 1999. Key milestones: somatostatin isolation (1973), discovery of unnatural GHRPs (1976), GHRH isolation (1982), the hypothesis that GHRPs reflect a new, undiscovered hormone (1984), demonstration of GHRP+GHRH synergy in humans (1990), discovery and cloning of the GHS/GHRP receptor (1996–1998), and finally ghrelin's isolation and identification by Kojima and Kangawa (1999).
A critical insight was that GHRPs release more growth hormone than GHRH when given intravenously in humans, but the reverse is true in laboratory cell cultures — suggesting GHRPs act on both the hypothalamus and pituitary, not just the pituitary. GHRPs are active by multiple routes (IV, subcutaneous, oral, intranasal), and ghrelin turned out to be pleiotropic, affecting not just growth hormone but also appetite, metabolism, cardiovascular function, immunity, and inflammation.
Bowers, Cyril Y · Historical Review
RPEP-01910 · 2012A substantial proportion of triple-negative breast cancers express receptors for both LHRH and GHRH, providing potential therapeutic targets. Potent antagonists of both GHRH and LHRH receptors have been developed and shown to inhibit tumor growth, tumorigenicity, and metastatic potential in experimental cancer models.
The targeted cytotoxic LHRH analog AN-152 (AEZS-108), which conjugates the chemotherapy drug doxorubicin to an LHRH peptide, delivers chemotherapy directly to LHRH receptor-expressing cancer cells. This approach could provide targeted treatment for TNBC while reducing systemic toxicity. The authors conclude that experimental evidence supports clinical trials with LHRH antagonists and AN-152 in TNBC patients.
Buchholz, Stefan; Seitz, Stephan; Engel, Jörg B; Montero, Alberto; Ortmann, Olaf; Perez, Roberto; Block, Norman L; Schally, Andrew V ·
RPEP-01912 · 2012BBS patients had significantly higher BMI than controls. Plasma levels of acylated ghrelin, total ghrelin, and obestatin were slightly elevated compared to controls, as was the acyl-to-total ghrelin ratio. Most notably, leptin levels were significantly elevated in BBS patients.
Normally, high leptin levels signal the brain to reduce appetite, and ghrelin should decrease after eating. In BBS patients, these negative feedback mechanisms appeared broken — ghrelin remained elevated despite adequate nutrition, and the body appeared resistant to leptin's appetite-suppressing effects. This shifts the hormonal balance toward constant hunger signaling.
Büscher, Anja K; Cetiner, Metin; Büscher, Rainer; Wingen, Anne-Margret; Hauffa, Berthold P; Hoyer, Peter F ·
RPEP-01918 · 2012Electroacupuncture at 60 Hz produced the strongest pain relief in goats, increasing pain threshold by 91%. This frequency uniquely triggered the simultaneous release of all three endogenous opioid peptides — met-enkephalin, β-endorphin, and dynorphin-A — across the broadest range of pain-related brain regions.
Lower frequencies (2 Hz) preferentially released met-enkephalin and β-endorphin, while high frequencies (80–100 Hz) favored dynorphin-A release. The 60 Hz frequency appeared to combine both patterns, activating more brain regions than any other frequency tested.
Cheng, Li-Li; Ding, Ming-Xing; Xiong, Cheng; Zhou, Min-Yan; Qiu, Zheng-Ying; Wang, Qiong · Animal
RPEP-01921 · 2012Animals classified as having extremely disrupted behavior (EBR) after predator-scent stress showed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala compared to minimally disrupted (MBR), partially disrupted (PBR), and unexposed control animals.
Critically, when NPY was administered centrally one hour after stress exposure, it significantly reduced the prevalence of extreme behavioral responses and decreased trauma-cue freezing behavior compared to vehicle controls. In contrast, an NPY-Y1-receptor antagonist did not provide protection, confirming the protective effect runs through NPY signaling.
Cohen, Hagit; Liu, Tianmin; Kozlovsky, Nitsan; Kaplan, Zeev; Zohar, Joseph; Mathé, Aleksander A · Animal Study
RPEP-01926 · 2012Earlier studies demonstrated that patients with chronic purulent rhinosinusitis have disturbances in cell-mediated immunity and defective monocyte chemotaxis (the ability of immune cells to migrate toward infection sites). Treatment with thymostimulin, a thymic hormone preparation, led to significant clinical improvement and in vitro restoration of monocyte chemotaxis.
With thymostimulin no longer available, thymosin alpha-1 has emerged as a potential alternative that has demonstrated some benefit for CPR. Current research focuses on understanding thymosin alpha-1's effects on monocyte function and gene expression profiles to clarify its mechanisms of action before future clinical trials.
Dalm, Virgil A S H; de Wit, Harm; Drexhage, Hemmo A ·
RPEP-01929 · 2012SV1 receptor immunoreactivity was detected in 44% (12 of 27) of oral squamous cell carcinomas compared to only 9% (3 of 33) of benign precancerous lesions (p<0.002). In cell culture, GHRH(1-29)NH2 and the GHRH agonist JI-38 stimulated HaCaT keratinocyte proliferation, and this growth stimulation was blocked by GHRH antagonists. The findings suggest SV1 expression may mark or contribute to malignant transformation in the oral epithelium.
Dioufa, Nikolina; Farmaki, Elena; Schally, Andrew V; Kiaris, Hippokratis; Vlahodimitropoulos, Dimitris; Papavassiliou, Athanasios G; Kittas, Christos; Block, Norman L; Chatzistamou, Ioulia ·
RPEP-01937 · 2012Cerebrolysin — a mixture of neurotrophic peptide fragments derived from pig brain proteins — significantly reduced oxidative stress-induced cell death (apoptosis) in human blood lymphocytes.
When cells from 10 healthy individuals were exposed to a pro-apoptotic stimulus (2-deoxy-D-ribose, which causes oxidative stress), Cerebrolysin significantly reduced the number of cells undergoing programmed death. However, Cerebrolysin had no significant effect on cells cultured under normal, unstressed conditions — meaning it specifically protected against oxidative damage rather than broadly stimulating cell survival. The researchers proposed that peripheral blood lymphocytes could serve as a convenient cell model for studying Cerebrolysin's neuroprotective mechanisms.
Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Muresanu, Dafin; Federico, Antonio · In Vitro
RPEP-01948 · 2012The central amygdala (CeA) is a critical brain region where neuropeptides modulate alcohol dependence. Acute alcohol suppresses excitatory glutamate transmission and enhances inhibitory GABA transmission in the CeA. Chronic alcohol exposure flips this pattern — glutamate transmission increases while GABA transmission also rises.
Pro-anxiety neuropeptides like CRF (corticotropin-releasing factor) and dynorphin increase GABAergic (inhibitory) signaling in the CeA, while anti-anxiety peptides like NPY (neuropeptide Y) and nociceptin decrease it. These peptides also modulate how alcohol affects CeA neurons — some enhance alcohol's effects, others block them.
Chronic alcohol produces lasting changes in these neuropeptide systems, which may drive the transition from casual drinking to dependence through negative reinforcement — drinking to avoid withdrawal-related anxiety rather than for pleasure.
Gilpin, Nicholas W; Roberto, Marisa · Review
RPEP-01949 · 2012Neuropeptide Y (NPY) in the central amygdala (CeA) plays a critical role in the transition to alcohol dependence. Mice lacking the NPY gene show both high anxiety and high alcohol drinking. Rats bred to prefer alcohol have baseline NPY deficits in the CeA, and infusing NPY into the CeA suppresses excessive drinking in both alcohol-preferring and alcohol-dependent rats. The author proposes that NPY modulates anxiety via Y2 receptor regulation of NPY release, while it reduces alcohol drinking via Y2 receptor regulation of GABA release — two distinct mechanisms through the same receptor.
Gilpin, Nicholas W · Review
RPEP-01952 · 2012In this randomized double-blind placebo-controlled single-dose trial with 8 males with Fragile X syndrome, intranasal oxytocin showed dose-dependent effects on different anxiety measures during a structured social challenge conducted 50 minutes after administration.
The 24 IU dose significantly improved eye gaze frequency — a key behavioral marker of social engagement that is severely impaired in Fragile X. The 48 IU dose significantly decreased salivary cortisol levels, indicating reduced physiological stress response. No significant effects were observed on heart rate, respiratory sinus arrhythmia (RSA), or heart rate variability (HRV), though individual heart rate data showed bidirectional responses (some participants increased, others decreased), suggesting oxytocin's effects may be individually variable.
Hall, Scott S; Lightbody, Amy A; McCarthy, Brigid E; Parker, Karen J; Reiss, Allan L ·
RPEP-01953 · 2012Teriparatide increased spine bone mineral density by 8.14% and hip BMD by 2.48% in postmenopausal women with osteoporosis. It reduced vertebral fracture risk by 70% (risk ratio 0.30) and non-vertebral fracture risk by 38% (risk ratio 0.62). Women who took more than 1,500 mg of calcium daily had significantly greater hip BMD gains (3.72% vs. 1.40%, p=0.004). Longer treatment duration did not appear to produce additional benefits.
Han, S-L; Wan, S-L ·
RPEP-01955 · 2012In this large double-blind, placebo-controlled trial of 1,070 patients with acute ischemic stroke in Asia, Cerebrolysin (30 mL daily IV for 10 days) failed to meet its primary endpoint — there was no significant difference between Cerebrolysin and placebo on a combined measure of stroke recovery scales.
However, a post hoc subgroup analysis of severely affected patients (NIHSS >12) showed a favorable trend: the Cerebrolysin group had better scores on both the NIHSS (OR 1.27) and modified Rankin Scale (OR 1.27). Most strikingly, 90-day mortality in this severe subgroup was 10.5% with Cerebrolysin versus 20.2% with placebo (hazard ratio 1.97, CI lower bound 1.00).
Heiss, Wolf-Dieter; Brainin, Michael; Bornstein, Natan M; Tuomilehto, Jaakko; Hong, Zhen · Randomized Controlled Trial
RPEP-01957 · 2012Among 98 children with growth or weight abnormalities, seven different sequence changes were identified in GHSR (two novel, five previously described), but none affected the protein-coding region. The ghrelin gene variant p.L72M was found in five patients but occurred at a higher rate in healthy controls, arguing against a pathogenic role.
Despite a high overall rate of sequence variations in both ghrelin and GHSR, none of the changes were functionally significant, indicating that mutations in these genes are not a common explanation for short stature, failure to thrive, growth hormone deficiency, or obesity in this population.
Hess, Ora; Admoni, Osnat; Khayat, Morad; Elias, Gadir; Almagor, Tal; Shalev, Stavit-Allon; Tenenbaum-Rakover, Yardena ·
RPEP-01960 · 2012Compared to a standard high-glycemic/low-protein breakfast, the soy protein meal replacement produced:
- Considerably lower glucose and insulin responses after eating
- Significantly less suppression of fat oxidation in the postprandial period — meaning the body kept burning fat rather than switching entirely to carbohydrate burning
- A 'second meal effect' where higher fat oxidation persisted even after a standardized lunch eaten 4 hours later
- Significantly lower ghrelin levels at 2 hours post-meal
- A trend toward higher PYY (peptide YY) levels, suggesting increased satiety signaling
These combined effects — lower insulin, more fat burning, reduced hunger hormone, and increased fullness signaling — provide a mechanistic explanation for why high-protein, low-glycemic meal replacements may help with weight management.
König, Daniel; Muser, Klaus; Berg, Aloys; Deibert, Peter ·
RPEP-01966 · 2012Combining cystatin C (a small peptide biomarker) with creatinine to estimate kidney filtration rate (GFR) is significantly more accurate than using either marker alone. The combined equation reduced errors by about a third — only 8.5% of estimates were off by more than 30%, compared to 12.8% for creatinine alone and 14.1% for cystatin C alone (both P<0.001).
Critically, for patients in the diagnostic gray zone (estimated GFR 45–74), the combined equation correctly reclassified 16.9% of those who appeared to have chronic kidney disease back to normal kidney function — preventing unnecessary diagnoses and treatments.
Inker, Lesley A; Schmid, Christopher H; Tighiouart, Hocine; Eckfeldt, John H; Feldman, Harold I; Greene, Tom; Kusek, John W; Manzi, Jane; Van Lente, Frederick; Zhang, Yaping Lucy; Coresh, Josef; Levey, Andrew S · Observational
RPEP-01970 · 2012Intranasal davunetide (NAP peptide) did not significantly improve cognitive test scores (MCCB) versus placebo in 63 people with schizophrenia over 12 weeks. However, it did significantly improve functional capacity — the ability to perform real-world tasks — as measured by the UPSA (p = 0.048).
The 5 mg dose showed stronger effects than 30 mg, with effect sizes of d = 0.74 for functional capacity and d = 0.34 for cognition. The peptide was well tolerated with no significant side effects. The authors estimated 45–50 subjects per group would be needed to detect significant cognitive effects in future trials.
Javitt, Daniel C; Buchanan, Robert W; Keefe, Richard S E; Kern, Robert; McMahon, Robert P; Green, Michael F; Lieberman, Jeffrey; Goff, Donald C; Csernansky, John G; McEvoy, Joseph P; Jarskog, Fred; Seidman, Larry J; Gold, James M; Kimhy, David; Nolan, Karen S; Barch, Deanna S; Ball, M Patricia; Robinson, James; Marder, Stephen R · Randomized Controlled Trial
RPEP-01971 · 2012Teduglutide, a GLP-2 analog, promotes intestinal mucosal growth and restores absorptive function in patients with short bowel syndrome (SBS), reducing their dependence on intravenous parenteral nutrition (PN). In a Phase II study, teduglutide reduced diarrhea by approximately 700 g/day and fecal energy losses by about 0.8 MJ/day over 3 weeks. Two Phase III randomized placebo-controlled 24-week trials confirmed these results, showing significant improvements in intestinal fluid absorption.
The drug works by enhancing the structural and functional integrity of remaining intestine — essentially making the surviving gut more efficient at absorbing nutrients and fluid. This translated to measurable reductions in the volume and frequency of parenteral support needed, significantly improving patients' quality of life.
Jeppesen, Palle Bekker · Review
RPEP-01973 · 2012After protein consumption, anorexigenic gut peptide hormones (CCK, GLP-1, peptide YY) are released from the gastrointestinal tract and communicate energy status to the brain via vagal nerve pathways. High-protein diets activate the nucleus tractus solitarius (brainstem) and arcuate nucleus (hypothalamus) more strongly than normal-protein diets.
Leucine specifically triggers two cellular energy sensors — mTOR (mammalian target of rapamycin) and AMPK (AMP-activated protein kinase) — contributing to protein's satiating effect. Additionally, high-protein diets reduce the hedonic response to food through effects on limbic reward circuits, decreasing the motivation to eat beyond metabolic need.
Journel, Marion; Chaumontet, Catherine; Darcel, Nicolas; Fromentin, Gilles; Tomé, Daniel ·
RPEP-01988 · 2012Complementary charged peptide sequences formed self-supporting hydrogels whose properties could be tuned through charge interactions, with the resulting materials supporting human fibroblast cell viability and proliferation.
Kyle, Stuart; Felton, Susan H; McPherson, Michael J; Aggeli, Amalia; Ingham, Eileen ·
RPEP-01991 · 2012The GHS-R exists in two isoforms: GHS-R1a (active, binds acyl-ghrelin) and GHS-R1b (inactive variant). GHS-R1b modulates the active receptor by forming heterodimeric complexes that reduce GHS-R1a trafficking to the cell surface — an important regulatory mechanism.
GHS-R1a expression extends far beyond the pituitary and hypothalamus to include other brain regions, pancreas, adipose tissue, immune cells, and the cardiovascular system. This distribution underlies ghrelin's pleiotropic effects: growth hormone secretion, appetite stimulation, learning and memory modulation, glucose and lipid metabolism regulation, inflammatory response control, and cardiac performance modulation. The review identifies cancer cachexia, age-related cognitive decline, obesity, and diabetes as conditions that could benefit from GHS-R1a agonists or antagonists.
Laviano, Alessandro; Molfino, Alessio; Rianda, Serena; Rossi Fanelli, Filippo ·
RPEP-01992 · 2012Co-administration of [D-Leu-4]-OB3, a synthetic leptin-like peptide, with exenatide resulted in mice that were 4.2% lighter than their starting weight after 14 days — a stark contrast to the 19.7% weight gain in control mice and the 13.9% gain with exenatide alone.
For blood glucose, co-delivery of [D-Leu-4]-OB3 with exenatide reduced levels by 38.3% (vs. 20.4% for exenatide alone), and co-delivery with pramlintide acetate reduced glucose by 50.5% (vs. 30.2% for pramlintide alone). Notably, the leptin-like peptide also moderated insulin levels, suggesting it may improve insulin sensitivity rather than simply driving more insulin secretion.
Leinung, Matthew C; Grasso, Patricia · Animal Study
RPEP-01993 · 2012The low-functioning NPSR1 Asn107 variant was significantly associated with schizophrenia (OR 1.19, p=0.017) in a case-control sample of 778 schizophrenia patients vs. 713 healthy controls. Patients homozygous for the Asn107 variant showed specifically decreased verbal memory consolidation (while memory acquisition was unaffected). Patients carrying the high-functioning Ile107 variant had significantly reduced startle amplitudes but unaffected prepulse inhibition and habituation.
These findings translate rodent NPS research into human psychiatric genetics — confirming that NPS receptor function affects both memory and startle response in schizophrenia patients, consistent with animal model predictions.
Lennertz, Leonhard; Quednow, Boris B; Schuhmacher, Anna; Petrovsky, Nadine; Frommann, Ingo; Schulze-Rauschenbach, Svenja; Landsberg, Martin W; Steinbrecher, Anja; Höfels, Susanne; Pukrop, Ralf; Klosterkötter, Joachim; Franke, Petra E; Wölwer, Wolfgang; Gaebel, Wolfgang; Häfner, Heinz; Maier, Wolfgang; Wagner, Michael; Mössner, Rainald ·
RPEP-01995 · 2012Both treatment groups (200U and 300U BTX-A) showed significant decreases in body weight and BMI (p<0.05). Gastric emptying times increased, particularly at 1 week post-treatment. Fasting ghrelin levels decreased significantly at 4 weeks after treatment. PYY levels decreased, especially at 12 weeks. Triglyceride levels also fell. No severe complications were observed across all 19 patients who completed follow-up.
Li, Li; Liu, Qing-Sen; Liu, Wen-Hui; Yang, Yun-Sheng; Yan, Dou; Peng, Li-Hua; Li, Lian-Yong; Meng, Jiang-Yun; Wang, Xiang-Dong; Ke, Meng ·
RPEP-02000 · 2012Two PEDF-derived peptide eye drops (P60, antiangiogenic; P78, neuroprotective) penetrated through the cornea and reached the retina within 1-4 hours when applied topically to diabetic mice. Both peptides reduced vascular leakage by ~60% and restored tight junction proteins (ZO1 and occludin) to non-diabetic levels. The neuroprotective P78 peptide reduced inflammatory cytokines (9 of 20 measured, including TNF-α, IL-6, and IFN-γ), prevented microglia activation by ~60%, reduced retinal ganglion cell death by ~22%, and prevented inner retinal thinning by ~13%. These effects were achieved with just once-weekly eye drops for 15 weeks.
Liu, Yanling; Leo, Lan Franco; McGregor, Corban; Grivitishvili, Anzor; Barnstable, Colin J; Tombran-Tink, Joyce ·
RPEP-02013 · 2012Neuromedin B (NMB) was identified in trigeminal ganglion sensory neurons that co-express CGRP and TRPV1, placing it in nociceptive (pain-sensing) circuits. Blocking NMB with an antagonist greatly attenuated edema and nerve sensitization caused by mustard oil stimulation, while direct NMB injection caused local swelling and pain sensitization.
The NMB receptor was found on interneurons in the superficial dorsal horn of the spinal cord. When these NMBR-expressing neurons were selectively destroyed using NMB-saporin, mice showed impaired responses to noxious heat but maintained normal responses to mechanical stimuli and itch, demonstrating NMB's selective role in thermal nociception.
Mishra, Santosh K; Holzman, Sarah; Hoon, Mark A ·
RPEP-02017 · 2012Lactoferrin binding protein B (LbpB) from two different Gram-negative bacterial species (Moraxella and Neisseria) provided protection against killing by human lactoferricin. The proposed mechanism involves clusters of negatively charged amino acids in the C-terminal lobe of LbpB that electrostatically interact with the positively charged (cationic) lactoferricin peptide, effectively sequestering it before it can insert into and disrupt the bacterial membrane.
The study also investigated the prevalence and sequence diversity of lactoferrin receptors across bacterial species, suggesting that LbpB-mediated defense against antimicrobial peptides is a widespread strategy among mucosal pathogens.
Morgenthau, Ari; Livingstone, Margaret; Adamiak, Paul; Schryvers, Anthony B ·
RPEP-02024 · 2012Copeptin, the C-terminal fragment of the arginine vasopressin precursor, serves as a stable and sensitive surrogate marker for vasopressin release. The review found that copeptin measurement is useful as a prognostic marker across multiple acute conditions seen in emergency departments, including lower respiratory tract infections, heart disease, and stroke.
The key advantage of copeptin over vasopressin itself is stability — vasopressin degrades rapidly in blood samples, making it difficult to measure accurately, while copeptin remains stable and can be reliably quantified with standard laboratory assays.
Nickel, Christian H; Bingisser, Roland; Morgenthaler, Nils G ·
RPEP-02026 · 2012Two new cyclic prodrugs of enkephalin opioid peptides (CA-[Cha(4), D-Leu(5)]-Enk and CA-[Cha(4), D-Ala(5)]-Enk) were designed and characterized:
- Structural success: NMR and molecular dynamics showed type I β-turn conformations favorable for transcellular permeation
- Physicochemical success: Higher lipophilicity than linear peptides (better for cell crossing)
- Metabolic success: Stable to cytochrome P-450 oxidative metabolism in intestinal mucosa
- Absorption failure: Caco-2 cell studies revealed the prodrugs are substrates for P-glycoprotein and other apically polarized efflux transporters
- In vivo confirmation: Rat intestinal perfusion confirmed poor intestinal permeation
Conclusion: Oral absorption of cyclic peptide prodrugs requires designing molecules that avoid both CYP enzyme metabolism AND efflux transporter recognition.
Nofsinger, Rebecca; Borchardt, Ronald T ·
RPEP-02029 · 2012Class B GPCRs share a common structural blueprint for peptide hormone recognition. The extracellular domain (ECD) provides high-affinity, specific binding through a conserved fold, while the seven-transmembrane domain handles receptor activation and G-protein coupling. Structural studies of multiple Class B GPCR ECDs revealed general principles governing how these receptors distinguish between different peptide hormones.
These structural insights have direct implications for designing peptide hormone analogs — understanding which parts of the peptide interact with the ECD versus the transmembrane domain helps researchers engineer modified peptides with improved selectivity, potency, or duration of action.
Pal, Kuntal; Melcher, Karsten; Xu, H Eric ·
RPEP-02031 · 2012D-[Lys3] GHRP-6 (DLS), widely used as a 'selective' ghrelin receptor antagonist, was unexpectedly found to also block the CXCR4 chemokine receptor. DLS blocked CXCL12 binding and signaling through CXCR4 on T cells and PBMCs. Because CXCR4 is a major co-receptor for HIV-1 entry into CD4+ cells, DLS partially blocked HIV-1 entry and replication in activated human PBMCs.
This means that many published studies using DLS as a 'specific' ghrelin receptor tool may have confounded results, as DLS has dual receptor activity. It also suggests that structural analogs of DLS could potentially block HIV infection, CXCR4-dependent cancer cell migration, and inflammatory immune cell trafficking.
Patel, Kalpesh; Dixit, Vishwa Deep; Lee, Jun Ho; Kim, Jie Wan; Schaffer, Eric M; Nguyen, Dzung; Taub, Dennis D ·
RPEP-02035 · 2012Treatment with the GHRH antagonist peptide MIA-602 significantly reduced tumor growth in mice bearing xenografts of two human TNBC cell lines (HCC1806 and MX-1).
Gene expression analysis revealed significant suppression of multiple inflammatory cytokines: IFNγ, IL-1α, IL-4, IL-6, IL-8, IL-10, and TNFα. These inflammatory cytokines are known to promote epithelial-mesenchymal transitions (EMT), drug resistance, and metastatic potential in breast cancer. siRNA silencing of GHRH receptors in vitro confirmed that the effects were receptor-mediated, inhibiting both GHRH-R genes and inflammatory cytokine expression.
Perez, Roberto; Schally, Andrew V; Vidaurre, Irving; Rincon, Ricardo; Block, Norman L; Rick, Ferenc G ·
RPEP-02036 · 2012GHRP-2 (growth hormone-releasing peptide-2) stimulated significant growth hormone release in 'little' (lit/lit) mice that have mutated, non-functional GHRH receptors — proving that GHRP-2 can trigger growth hormone release independently of the GHRH signaling pathway. Lit/lit mice injected with 10 mcg GHRP-2 released 9.3±1.5 ng/ml GH vs 1.04±1.15 ng/ml in controls (p<0.001).
Heterozygous lit/+ mice showed intermediate GH release (34.5±9.7 ng/ml), while wild-type mice had the highest response (163±46 ng/ml). This dose-response pattern across genotypes demonstrates that GHRP-2's effect is partially but not fully dependent on GHRH signaling — it works through a separate pathway via the ghrelin receptor (GHS-R1a) on remaining pituitary somatotroph cells.
Peroni, Cibele N; Hayashida, Cesar Y; Nascimento, Nancy; Longuini, Viviane C; Toledo, Rodrigo A; Bartolini, Paolo; Bowers, Cyril Y; Toledo, Sergio P A · Animal Study
RPEP-02040 · 2012The stapled conantokin-G analog conG[11-15,S(i,i+4)S(8)] demonstrated:
- Potent NR2B-selective NMDA receptor antagonism: IC50 = 0.7 μM
- Significant protection in the 6-Hz psychomotor seizure model (a model specifically designed to detect efficacy against drug-resistant epilepsy)
- No behavioral motor toxicity (unlike native conantokin-G)
- Enhanced helical conformation in metal-free environments (confirmed by circular dichroism and molecular modeling)
- NMR confirmed single Z-configuration olefinic bond from ring-closing metathesis
The i,i+4 staple positioning successfully replaced the γ-carboxyglutamic acid residues' metal-chelation function while preserving pharmacological activity.
Platt, Randall J; Han, Tiffany S; Green, Brad R; Smith, Misty D; Skalicky, Jack; Gruszczynski, Pawel; White, H Steve; Olivera, Baldomero; Bulaj, Grzegorz; Gajewiak, Joanna ·
RPEP-02041 · 2012Oxyntomodulin (OXM) is a gut-derived peptide that acts as a dual agonist of both the GLP-1 receptor and the glucagon receptor. This review summarizes evidence that OXM injections in humans cause significant reductions in weight and appetite while increasing energy expenditure — a combination that single GLP-1 receptor agonists don't fully achieve. Although glucagon receptor activation normally raises blood sugar (potentially harmful in diabetics), the simultaneous GLP-1 receptor activation counteracts this effect. In diet-induced obese mice, OXM improved glucose tolerance. The dual agonist approach may offer enhanced weight loss and better glycemic control compared to GLP-1 agonists alone.
Pocai, Alessandro ·
RPEP-02042 · 2012Researchers successfully produced self-assembling β-structured peptides (the P₁₁ family) using a SUMO fusion protein system in bacteria, achieving high yields with 46–99% peptide recovery after cleavage. The recombinant peptides behaved identically to chemically synthesized versions in self-assembly and biophysical assays, demonstrating this as a viable alternative production method for hydrogel-forming peptides used in tissue engineering.
Prakash, Abhinav; Parsons, Stephen J; Kyle, Stuart; McPherson, Michael J · Laboratory
RPEP-02045 · 2012When hen egg white lysozyme was digested in a simulated gut environment, the resulting peptide fragments showed strong ACE-inhibitory activity with an IC50 of 12.6 μg/ml — meaning a very low concentration was needed to block half the activity of the blood-pressure-raising enzyme ACE. The digest also showed remarkable antioxidant activity.
Using mass spectrometry, the researchers identified 38 distinct peptides in the digest. Several of these matched the known structural requirements for ACE inhibition and antioxidant function, suggesting egg white lysozyme is a rich source of multifunctional bioactive peptides.
Rao, Shengqi; Sun, Jun; Liu, Yuntao; Zeng, Huawei; Su, Yujie; Yang, Yanjun · In Vitro Study
RPEP-02046 · 2012The review identifies specific nutrient receptors expressed on enteroendocrine cells in the gut: T1R1/T1R3, calcium-sensing receptor, and GPR93 for amino acids and protein; GPR40, GPR41, GPR43, and GPR120 for fatty acids; and T1R2/T1R3 for sugars. These receptors serve a dual function: regulating nutrient transporter expression to control absorption, and directly stimulating secretion of gastrointestinal peptides (CCK, GLP-1, PYY) into the lamina propria.
These peptide signals are transmitted to brain centers controlling feeding behavior (hypothalamus and nucleus of the solitary tract) primarily via vagal nerve afferents, forming the first signal of satiation. The review also notes that tastant compounds — not just full nutrient molecules — can trigger gut peptide secretion via chemosensory receptors on enteroendocrine cells.
Rasoamanana, Rojo; Darcel, Nicolas; Fromentin, Gilles; Tomé, Daniel ·
RPEP-02050 · 2012Alpha-melanocyte-stimulating hormone (α-MSH) activated approximately 70% of GnRH neurons through direct postsynaptic melanocortin receptor 3 and 4 signaling. NPY had complex, receptor-specific effects: Y1 receptors suppressed GnRH neuron activity (~45% inhibited by porcine NPY), while Y4 receptors were stimulatory (~56% excited by a Y1/Y4/Y5 agonist). A small subset of GnRH neurons (~15%) was excited by CART peptide, and β-endorphin inhibited a similar proportion.
Agouti-related peptide showed variable effects, inhibiting ~10% and stimulating ~25% of GnRH neurons. These findings demonstrate that metabolic-sensing neurons regulate fertility neurons through multiple neuropeptide pathways acting in parallel.
Roa, Juan; Herbison, Allan E ·
RPEP-02052 · 2012Protegrin-1 (PG-1) inhibited dengue NS2B-NS3 serine protease with an IC₅₀ of 11.7 μM. When tested against dengue serotype-2 (DENV-2) replication in MK2 cells, graded concentrations of PG-1 at non-toxic doses significantly reduced viral replication (p < 0.001) at 24, 48, and 72 hours post-infection.
The percentage of inhibition was significantly higher at 24 hours compared to 48 and 72 hours (p < 0.01), suggesting PG-1 is most effective in the early stages of viral replication. The peptide was synthesized with correct disulphide bond formation confirmed by LC-MS and RP-HPLC.
Rothan, Hussin A; Abdulrahman, Ammar Y; Sasikumer, Pottayil G; Othman, Shatrah; Rahman, Noorsaadah Abd; Yusof, Rohana ·
RPEP-02058 · 2012Substance P (SP) and CGRP-positive nerve fibers were identified around large vessels of the medialis superior alveolar branches and within the floor region of the maxillary sinus. The floor region contained particularly complex branching networks of these neuropeptide-containing fibers. These findings provide an anatomical map of pain- and inflammation-mediating nerve fibers relevant to sinus floor elevation surgery.
Sato, Iwao; Imura, Kosuke; Miwa, Yoko; Yoshida, Shunji; Sunohara, Masataka ·
RPEP-02074 · 2012Both exenatide and liraglutide improved glycemic control as monotherapy and in combination with oral agents, providing additive effects in dual and triple therapy regimens. In head-to-head clinical trials, liraglutide achieved greater reductions in HbA1c and fasting plasma glucose, while exenatide had greater effects on postprandial glucose levels.
Both agents demonstrated statistically significant weight reduction and small beneficial effects on blood pressure, with unchanged lipid profiles. The review positioned GLP-1 receptor agonists as a treatment option that could address multiple cardiometabolic parameters beyond glycemic control alone.
Spellman, Craig W ·
RPEP-02083 · 2012The neuropeptide PACAP (pituitary adenylate cyclase activating polypeptide) significantly protected the retina from diabetes-induced damage when injected into the eyes of diabetic rats. In untreated diabetic retinas, cone photoreceptors degenerated, dopaminergic nerve cells were lost, ganglion cell numbers declined, and glial cells showed stress responses.
PACAP treatment reversed these structural changes — it preserved cone photoreceptors and their outer segments, maintained ganglion cell numbers, and upregulated the PAC1 receptor and tyrosine hydroxylase (an enzyme critical for dopamine production). The protection appears to work through PACAP's PAC1 receptor.
Szabadfi, Krisztina; Atlasz, Tamas; Kiss, Peter; Reglodi, Dora; Szabo, Aliz; Kovacs, Krisztina; Szalontai, Balint; Setalo, Gyorgy; Banki, Eszter; Csanaky, Katalin; Tamas, Andrea; Gabriel, Robert · Animal Study
RPEP-02084 · 2012GHRH antagonists MZ-4-71 and JV-1-36 effectively blocked GHRH-stimulated growth hormone secretion from human pituitary adenoma cells. When tumor cells were exposed to GHRH pulses, GH levels rose 3- to 5-fold above baseline. Both antagonists completely prevented this stimulatory response.
Importantly, neither GHRH antagonist affected baseline GH secretion, indicating the tumor cells were not producing GHRH themselves in an autocrine loop — they were responding to external GHRH signals. The somatostatin analog RC-160 showed similar inhibitory effects and was more potent than natural somatostatin-14. The study also confirmed abundant expression of the GHRH receptor and its splice variant SV1 in the adenoma tissue.
Szalontay, Luca; Benveniste, Ronald J; Schally, Andrew V; Vidaurre, Irving; Nadji, Mehrdad; Zarandi, Marta; Block, Norman L; Kovacs, Magdolna ·
RPEP-02096 · 2012Crude INSL6[151-161] peptide (~70% purity) triggered contractile responses in guinea pig ileum smooth muscle preparations. However, when the same peptide was purified to ≥95% purity, it showed no biological activity whatsoever in the same model.
Crude peptide materials from multiple suppliers (50-80% purity) all produced false-positive results, confirming that the activity came from synthesis by-products rather than the target peptide. This demonstrates that impurity profiles from peptide synthesis can produce entirely misleading biological conclusions — a critical quality control issue for the peptide research field.
Verbeken, Mathieu; Wynendaele, Evelien; Lefebvre, Romain A; Goossens, Els; Spiegeleer, Bart De ·