RPEP-06722 · 2023Freshly isolated rat renal cells were validated as an effective screening tool for evaluating kidney uptake of radiolabeled peptides. The cells maintained functional megalin transport systems (a key driver of renal peptide accumulation), confirmed by colocalization experiments showing proximal tubular cells bearing megalin. The method was successfully tested with indium-111 and lutetium-177 labeled analogs of somatostatin and gastrin, demonstrating its applicability for comparative renal accumulation studies.
Barta, Pavel; Nachtigal, Petr; Maixnerova, Jana; Zemankova, Lenka; Trejtnar, Frantisek ·
RPEP-06723 · 2023Peptides derived from enzymatic hydrolysis of rainbow trout protein demonstrated three types of biological activity in vitro: antioxidant effects (confirmed by DPPH, FRAP, ORAC, and ABTS assays), dose-dependent ACE inhibition (relevant to blood pressure), and DPP-IV inhibition of up to 27.57 ± 3.7% at 5 mg/mL (relevant to blood sugar regulation). These activities were confirmed at the cellular level using human intestinal Caco-2 cells, where the hydrolysate reduced hydrogen peroxide-induced reactive oxygen species and lipid peroxidation.
Bartolomei, Martina; Cropotova, Janna; Bollati, Carlotta; Kvangarsnes, Kristine; d'Adduzio, Lorenza; Li, Jianqiang; Boschin, Giovanna; Lammi, Carmen ·
RPEP-06726 · 2023In an ovalbumin-induced allergic rhinitis rat model, aprepitant (a substance P receptor antagonist) failed to reduce nasal symptoms like scratching and sneezing, while antihistamines and leukotriene receptor antagonists (LTRA) significantly improved those symptoms.
However, aprepitant did produce histopathological changes — it significantly reduced pseudostratification (abnormal cell layering) in the laryngeal mucosa compared to untreated allergic rats. The study also found that the allergic rhinitis model produced measurable allergic changes in the larynx, not just the nose.
Becerik, Çağrı; Karaca, Çiğdem T; Özcan, Zühal; Kul, Selim; Toros, Sema Z · Animal Study
RPEP-06733 · 2023Albumin was isolated from C. striata fish extract using the Cohn Process, yielding 3.8 ± 2.1% in the most albumin-rich fraction (Fraction-5). Two protein bands of approximately 10 and 13 kDa were identified by tricine-SDS PAGE.
ACE inhibition activity increased across fractions, ranging from 7.09% to 22.99%. The highest ACE-inhibiting activity was found in peptides produced by alcalase hydrolysis with molecular size under 3 kDa, achieving an IC50 of 36.93 μg/mL. This was statistically significant compared to non-hydrolyzed fractions, supporting the potential of C. striata albumin-derived peptides as natural antihypertensive agents.
Berlian, Guntur; Riani, Catur; Kurniati, Neng Fisheri; Rachmawati, Heni ·
RPEP-06736 · 2023Researchers extracted peptides from moth bean seeds using six different enzymes and found that alcalase produced the most effective ACE-inhibiting fragments. The most potent peptide fraction inhibited ACE at just 11.19 ± 0.15 μg/mL. Four specific peptides (IAWDFR, ADLPGLK, DKPWWPK, and AVIPNAPNLR) were identified through mass spectrometry, with molecular docking showing two bind to active sites and two to non-active sites of the ACE molecule.
In live testing, the moth bean protein hydrolysate lowered systolic blood pressure in hypertensive rats from 155 ± 3.13 mmHg (control) to 125 ± 0.76 mmHg — a 30 mmHg reduction.
Bhadkaria, Amita; Narvekar, Dakshita Tanaji; Nagar, D P; Sah, Sangeeta Pilkwal; Srivastava, Nidhi; Bhagyawant, Sameer Suresh · Animal Study
RPEP-06737 · 2023Human cathelicidin LL-37 neutralized multiple SARS-CoV-2 variants through direct disruption of the viral membrane, as confirmed by biophysical and computational studies. Niacinamide enhanced this antiviral activity through its hydrotropic action, which may increase the bioavailability of LL-37.
Clinically, an inverse correlation was observed between LL-37 levels and COVID-19 disease severity in patients — those with higher LL-37 levels had milder disease. The combination of niacinamide and LL-37 showed potent antiviral activity against various SARS-CoV-2 variants, including those that escape vaccine-generated immunity.
Bhatt, Tanay; Dam, Binita; Khedkar, Sneha Uday; Lall, Sahil; Pandey, Subhashini; Kataria, Sunny; Ajnabi, Johan; Gulzar, Shah-E-Jahan; Dias, Paul M; Waskar, Morris; Raut, Janhavi; Sundaramurthy, Varadharajan; Vemula, Praveen Kumar; Ghatlia, Naresh; Majumdar, Amitabha; Jamora, Colin ·
RPEP-06746 · 2023Across real-world studies published between 2010 and 2020:
• OnabotulinumtoxinA: 55 studies with long-term data (>1 year, up to 3 years). Substantial evidence for reducing headache number/frequency, decreasing acute medication use, and improving well-being and daily activity.
• Erenumab (CGRP mAb): 6 studies with data up to 6 months. More limited evidence showing benefits for the same parameters.
• Multiple CGRP mAbs: 1 study with data up to 12 months. Single study suggesting reduced headache frequency and impact.
• Topiramate: 1 study with data up to 3 months. Single study suggesting decreased headache frequency.
OnabotulinumtoxinA was the only treatment with long-term safety data from real-world settings reporting treatment-related adverse events.
Blumenfeld, Andrew M; Kaur, Gavneet; Mahajan, Anadi; Shukla, Hemlata; Sommer, Katherine; Tung, Amy; Knievel, Kerry L ·
RPEP-06748 · 2023Thymosin beta-4 demonstrated multiple regenerative effects in the heart:
- In embryonic mice: TB4 is expressed in the developing heart and promotes cardiac cell migration and survival
- After heart attack: systemic TB4 injections enhanced myocyte (heart muscle cell) survival and improved cardiac function following coronary artery ligation
- In uninjured adults: intravenous TB4 altered adult epicardial morphology to resemble embryonic characteristics, increased cardiac vessel number, and shifted gene expression toward an embryonic profile
- TB4 activated epicardial progenitor cells independent of hypoxic injury, suggesting regenerative effects don't require prior damage
The reactivation of an embryonic developmental program in adult tissue is the key conceptual advance — it suggests that developmentally relevant peptides could potentially reverse age-related cellular changes.
Bock-Marquette, Ildiko; Maar, Klaudia; Maar, Szabolcs; Lippai, Balint; Faskerti, Gabor; Gallyas, Ferenc; Olson, Eric N; Srivastava, Deepak ·
RPEP-06750 · 2023This review consolidates research from 2021 across 18 major topic areas related to endogenous opioid peptides: molecular/biochemical studies, animal and human pain/analgesia, nonopioid analgesics, tolerance and dependence, stress and social status, learning and memory, eating and drinking, drug abuse and alcohol, sexual activity and hormones, mental illness and mood, seizures, neurophysiology, locomotion, gastrointestinal/renal/hepatic function, cardiovascular responses, respiration and thermoregulation, and immunological responses.
As a comprehensive anthology, the review does not present a single finding but rather synthesizes the state of the field across all behavioral dimensions of opioid peptide research from a single year.
Bodnar, Richard J ·
RPEP-06751 · 2023Daily subcutaneous MR-409 treatment from postnatal day 2 to day 12 in SMNΔ7 SMA mice produced multiple beneficial effects, particularly at 2 mg/kg:
- Increased body weight and improved motor behavior
- Reduced muscle atrophy with increased fiber size in quadriceps and gastrocnemius
- Upregulated myogenic genes and inhibited proteolytic (muscle-degrading) pathways
- Promoted neuromuscular junction maturation (fewer multi-innervated endplates, more mono-innervated)
- Delayed alpha motor neuron death in the spinal cord
- Reduced neuroinflammation in the spinal cord
The breadth of effects — spanning muscle, nerve, and immune pathways — suggests GHRH agonists target multiple aspects of SMA pathology simultaneously.
Boido, Marina; Gesmundo, Iacopo; Caretto, Anna; Pedrolli, Francesca; Schellino, Roberta; Leone, Sheila; Cai, Renzhi; Sha, Wei; Ghigo, Ezio; Schally, Andrew V; Vercelli, Alessandro; Granata, Riccarda · Animal Study
RPEP-06755 · 2023Dulaglutide 1.5 mg reduced the risk of kidney function-related outcomes by 25% compared to placebo (HR 0.75, 95% CI 0.62–0.92, p = 0.004) in nearly 10,000 people with type 2 diabetes. Specifically, sustained ≥40% eGFR decline occurred 28% less frequently with dulaglutide (HR 0.72, p = 0.002).
The annual rate of kidney function decline was significantly slower with dulaglutide (-1.37 vs -1.56 mL/min/1.73 m²/year, p < 0.001). Importantly, the kidney-protective effect was consistent regardless of baseline kidney function or albumin levels — meaning it benefited patients across the spectrum of kidney health.
Botros, Fady T; Gerstein, Hertzel C; Malik, Raleigh; Nicolay, Claudia; Hoover, Anastasia; Turfanda, Ibrahim; Colhoun, Helen M; Shaw, Jonathan E · Post Hoc Analysis
RPEP-06759 · 2023ARNi (angiotensin receptor-neprilysin inhibitor) therapy effectively reduces death and hospitalization in heart failure patients with NYHA functional class II-III symptoms. However, clinical trials failed to show benefits when compared to ACE inhibitors or ARBs in two populations: patients with advanced HF with reduced ejection fraction, and post-MI patients with left ventricular dysfunction but without HF. The review proposes that in advanced HF, downstream blunting of natriuretic peptide response limits efficacy, while post-MI patients without HF may not need increased natriuretic peptide availability.
Bozkurt, Biykem; Nair, Ajith P; Misra, Arunima; Scott, Claire Z; Mahar, Jamal H; Fedson, Savitri ·
RPEP-06760 · 2023The review establishes two main categories of peptide-based anti-obesity therapies:
1. GLP-1 receptor agonists work by stimulating satiety hormone secretion and are effective for obesity driven by excessive calorie intake. These are now among the most successful obesity treatments.
2. Emerging genetic-targeted therapies address specific molecular defects: leptin analogs restore function in generalized lipodystrophy and related conditions, while melanocortin-4 receptor (MC4R) agonists target defects in the MC4R signaling pathway that regulates energy balance and appetite. These therapies fill a gap where conventional weight loss strategies fail — genetic obesity conditions like Bardet-Biedl syndrome and POMC deficiency.
Brandfon, Skyler; Eylon, Adi; Khanna, Deepesh; Parmar, Mayur S ·
RPEP-06761 · 2023Multiple chicken slaughterhouse byproducts — including blood, bones, skins, and especially chicken feet — can be enzymatically broken down into protein hydrolysates containing peptides with ACE-inhibitory activity and blood pressure-lowering effects in animal models. The underlying mechanisms include increased endogenous antioxidant levels, reduced ACE activity, and improved endothelial dysfunction. However, clinical confirmation in humans is still lacking.
Bravo, Francisca Isabel; Calvo, Enrique; López-Villalba, Rafael A; Torres-Fuentes, Cristina; Muguerza, Begoña; García-Ruiz, Almudena; Morales, Diego ·
RPEP-06762 · 2023Dual and triple agonists show effectiveness on NAFLD biomarkers, but most studies are ongoing.
Brodosi, Lucia; Petroni, Maria Letizia; Marchesini, Giulio ·
RPEP-06764 · 2023A synthetic peptide fragment called JB2, derived from insulin-like growth factor binding protein 2 (IGFBP2), rescued multiple deficits in a mouse model of Phelan-McDermid Syndrome (PMS) — a genetic form of autism. JB2 restored synaptic function and plasticity, improved learning and memory, normalized vocalizations and motor function, reduced seizure susceptibility, and corrected abnormal brainwave patterns (EEG measures) that are directly translatable to human testing.
Mechanistically, JB2 binds directly to synapses and dendrites, activating NMDA receptors and IGF2 receptors (but not IGF1 receptors) to trigger gene expression and extensive remodeling of the phosphoproteome. Among the affected proteins, autism risk factors and Shank3-associated networks were significantly enriched — suggesting JB2 directly targets the molecular pathways disrupted in PMS and broader ASD.
Burgdorf, Jeffrey S; Yoon, Sehyoun; Dos Santos, Marc; Lammert, Catherine R; Moskal, Joseph R; Penzes, Peter · Animal Study
RPEP-06766 · 2023The sodium-alginate microparticles achieved encapsulation efficiency above 80% across all formulations, meaning the vast majority of insulin was successfully trapped inside the beads. The pH-responsive alginate polymer protected insulin in acidic conditions (mimicking the stomach) and released it at higher pH (mimicking the intestine).
After 120 minutes in simulated intestinal fluid containing digestive enzymes, 66% of the insulin remained intact — a meaningful improvement over unprotected insulin. Permeability testing using Caco-2 intestinal cell models showed that formulations containing the surfactant-based permeation enhancers (Labrasol ALF and Labrafil M 2125 CS at 0.10% v/v) significantly increased insulin transport across the cell layer compared to a control insulin solution.
Bácskay, Ildikó; Papp, Boglárka; Pártos, Péter; Budai, István; Pető, Ágota; Fehér, Pálma; Ujhelyi, Zoltán; Kósa, Dóra ·
RPEP-06769 · 2023A 9-amino-acid peptide (sequence HEAEDLFYQ, residues 34–42 of ACE2 α-helix 1) was chemically stapled using ring-closing metathesis at the i to i+4 positions. This stapled peptide competed with recombinant ACE2 for binding to the SARS-CoV-2 Spike receptor-binding domain (RBD) at micromolar concentrations in a colorimetric ELISA assay.
Circular dichroism studies confirmed the ring-closing metathesis staple stabilized the helical structure more effectively than an alternative triazole staple produced by click chemistry. Molecular dynamics simulations further showed the stapled peptide not only bound the Spike RBD and sterically interfered with ACE2 binding, but displayed higher affinity for the target than the unstapled parent epitope.
Calugi, Lorenzo; Sautariello, Giulia; Lenci, Elena; Mattei, Mauro Leucio; Coppa, Crescenzo; Cini, Nicoletta; Contini, Alessandro; Trabocchi, Andrea ·
RPEP-06782 · 2023From a systematic search of 3,668 articles, 62 studies met inclusion criteria and identified eight established single peptide biomarkers plus several proteomic classifiers (including CKD273 and IgAN237) for chronic kidney disease. These urinary peptide biomarkers show potential to detect kidney disease earlier than the current standard tests — serum creatinine and urinary albumin — which have known blind spots in early-stage kidney impairment.
Proteomic classifiers that analyze patterns across hundreds of peptides simultaneously (like CKD273, which uses 273 urinary peptides) are emerging as the most promising approach for clinical implementation.
Catanese, Lorenzo; Siwy, Justyna; Mischak, Harald; Wendt, Ralph; Beige, Joachim; Rupprecht, Harald · Systematic Review
RPEP-06788 · 2023Among the panel of stapled Macropin-1 variants synthesized, Mac-1-sp4 demonstrated the most comprehensive improvements: enhanced α-helical structure, greater resistance to protease degradation, improved cell membrane permeability, stronger induction of cancer cell apoptosis, in vivo antitumor activity against breast cancer, and inhibition of tubulin polymerization — the protein assembly process required for cell division.
The hydrocarbon stapling modification successfully addressed the two main limitations of the natural linear peptide: its inability to efficiently cross cell membranes and its vulnerability to enzymatic breakdown.
Chen, Baobao; Li, Yinghua; Bai, Haohao; Ji, Yajing; Cong, Wei; Hu, Honggang; He, Shipeng ·
RPEP-06789 · 2023The network meta-analysis of 12 RCTs covering 6,213 patients and 10 GLP-1RA regimens produced a clear efficacy ranking for HbA1c reduction: Semaglutide 2.0mg > Semaglutide 1.0mg > Dulaglutide 4.5mg > Semaglutide 0.5mg > Dulaglutide 3.0mg > PEX168 200μg > Dulaglutide 1.5mg > PEX168 100μg > Dulaglutide 0.75mg. All once-weekly GLP-1RAs were significantly better than placebo.
Safety analysis showed comparable hypoglycemia risk across all regimens, and all long-acting GLP-1RAs (except PEX168) had lower rates of diarrhea, nausea, and vomiting than placebo.
Chen, Han; Li, Xin-Zhu; Chen, Jia-Qing; Ren, Tian-Shu; Zhang, Ying-Shi; Wang, Yi-Nuo; Zhao, Qing-Chun ·
RPEP-06794 · 2023Cyclic peptides have improved stability and bioavailability, making them viable PPI modulators.
Cheng, Jiongjia; Zhou, Junlong; Kong, Lingyan; Wang, Haiying; Zhang, Yuchi; Wang, Xiaofeng; Liu, Guangxiang; Chu, Qian ·
RPEP-06795 · 2023Semaglutide showed significantly higher signals for misuse-related adverse events compared to other GLP-1 drugs. Its proportional reporting ratios (PRR) for 'drug abuse' (4.05), 'drug withdrawal syndrome' (4.05), 'prescription drug used without a prescription' (3.60), and 'intentional product use issue' (1.80) were all significantly elevated (p<0.01) versus other GLP-1 receptor agonists.
However, when compared to the phentermine-topiramate combination (an established weight loss drug with known misuse potential), semaglutide showed no significant differences in misuse signals. This suggests semaglutide's misuse signal may be in line with other weight loss medications rather than uniquely problematic.
Chiappini, Stefania; Vickers-Smith, Rachel; Harris, Daniel; Papanti Pelletier, G Duccio; Corkery, John Martin; Guirguis, Amira; Martinotti, Giovanni; Sensi, Stefano L; Schifano, Fabrizio · Pharmacovigilance / Database Analysis
RPEP-06797 · 2023Fish collagen peptide supplementation produced comprehensive anti-photoaging effects across both in vitro and in vivo UV-B models:
- Increased hyaluronic acid, sphingomyelin, and overall skin hydration by upregulating hyaluronic acid synthases 1-3, serine palmitoyltransferase 1, and ceramide synthase 4
- Reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) by suppressing IκBα, p65, and COX-2 protein expression
- Boosted antioxidant enzyme activities
- Downregulated collagen-degrading MMP-1, -2, and -9 pathways through JNK/c-Fos/c-Jun suppression
- Upregulated new collagen production via TGF-β receptor I, collagen type I, procollagen type I, and Smad signaling
Cho, Wonhee; Park, Jeongjin; Lee, Minhee; Park, Seong-Hoo; Jung, Jaeeun; Kim, Jinhak; Eun, Sangwon; Kim, Jinkyung ·
RPEP-06798 · 2023The low-molecular-weight fish collagen peptide (VGPHGPAG) demonstrated dual protective mechanisms:
**Anti-catabolic effects:**
- Increased aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3 (protective matrix components)
- Decreased phosphorylation of Smad, MMP-3, and MMP-13 (destructive enzymes)
**Anti-inflammatory and anti-apoptotic effects:**
- Suppressed inflammation pathways in LPS-treated chondrocytes and MIA-induced OA cartilage
- Suppressed apoptosis pathways, preventing chondrocyte death
These effects were consistent across both in vitro (H₂O₂ or LPS-treated primary chondrocytes) and in vivo (MIA-injected rat osteoarthritis) models.
Cho, Wonhee; Park, Jeongjin; Kim, Jinhee; Lee, Minhee; Park, So Jung; Kim, Kyung Seok; Jun, Woojin; Kim, Ok-Kyung; Lee, Jeongmin ·
RPEP-06802 · 2023Researchers fermented whey protein concentrate using a co-culture of Lactobacillus paracasei and Saccharomyces cerevisiae (yeast) and identified novel peptides with ACE-inhibitory (blood pressure lowering), antioxidant, and anti-inflammatory properties. Maximum proteolytic activity was 6.50 mg/mL at 37°C and 8.59 mg/mL at 25°C after 48 hours of fermentation.
Two specific peptides — AFLDSRTR and ILGAFIQIITFR — were identified and characterized. Molecular docking showed they interact with human myeloperoxidase, an enzyme involved in inflammation. The whey fermentate also reduced inflammation in macrophage cell cultures exposed to bacterial toxins (LPS).
Chopada, Keval; Basaiawmoit, Bethsheba; Sakure, Amar A; Maurya, Ruchika; Bishnoi, Mahendra; Kondepudi, Kanthi Kiran; Solanki, Divyang; Singh, B P; Padhi, Srichandan; Rai, Amit Kumar; Liu, Zhenbin; Mishra, B K; Hati, Subrota · In Vitro
RPEP-06805 · 2023Semaglutide demonstrated broad anti-alcohol effects across models and species:
- Dose-dependently reduced binge-like alcohol drinking in mice (drinking-in-the-dark model)
- Also reduced intake of other caloric/noncaloric solutions, suggesting a general reward-reducing effect
- Reduced binge-like and dependence-induced alcohol drinking in rats
- Effects observed in both male and female animals
Mechanistically, semaglutide increased spontaneous inhibitory postsynaptic current (sIPSC) frequency in central amygdala (CeA) and infralimbic cortex (ILC) neurons from alcohol-naive rats, indicating enhanced GABA release. However, this effect was absent in alcohol-dependent rats, suggesting chronic alcohol exposure may alter GLP-1 receptor-GABA interactions.
Chuong, Vicky; Farokhnia, Mehdi; Khom, Sophia; Pince, Claire L; Elvig, Sophie K; Vlkolinsky, Roman; Marchette, Renata Cn; Koob, George F; Roberto, Marisa; Vendruscolo, Leandro F; Leggio, Lorenzo ·
RPEP-06808 · 2023Daily subcutaneous MIA-602 treatment in rVSV-SARS-CoV-2-infected K18-hACE2 transgenic mice produced: weight recovery (vs. continued loss in vehicle group), reduced lung perivascular inflammation and pneumonia, decreased ICAM-1 expression in both lung and heart tissue, rescued respiratory rate and normalized airflow parameters (Penh, Rpef, expiratory parameters), and normalized inflammation and necroptosis markers (ZBP1, pMLKL) that were heightened by infection. RNASeq analysis confirmed an anti-inflammatory and pro-survival mechanism of action. The rVSV-SARS-CoV-2 model showed similar pathology to native SARS-CoV-2 infection (~60% infectivity).
Condor Capcha, Jose M; Kamiar, Ali; Robleto, Emely; Saad, Ali G; Cui, Tengjiao; Wong, Amanda; Villano, Jason; Zhong, William; Pekosz, Andrew; Medina, Edgar; Cai, Renzhi; Sha, Wei; Ranek, Mark J; Webster, Keith A; Schally, Andrew V; Jackson, Robert M; Shehadeh, Lina A ·
RPEP-06809 · 2023The double-stapled peptide FRNC-1 is the first orally effective peptide validated as a therapeutic candidate for postmenopausal osteoporosis. It inhibited bone resorption by mature osteoclasts through specific inhibition of phosphorylated GSK-3β, showed markedly improved helical content and proteolytic resistance compared to its linear form, and effectively prevented osteoclast activation and improved bone density in ovariectomized mice after both intravenous and oral (intragastric) administration.
Cong, Wei; Shen, Huaxing; Liao, Xiufei; Zheng, Mengjun; Kong, Xianglong; Wang, Zhe; Chen, Si; Li, Yulei; Hu, Honggang; Li, Xiang ·
RPEP-06812 · 2023Pramlintide (delivered systemically via IP injection) improved cognitive function in APP/PS1 Alzheimer's model mice even when central amylin receptors were simultaneously blocked with AC187 (delivered ICV). This suggests pramlintide's cognitive benefits operate through peripheral metabolic mechanisms rather than direct central receptor activation.
Central amylin receptor inhibition with AC187 increased amyloid-beta pathology in female APP/PS1 mice — an effect mitigated by peripheral pramlintide. Transcriptomic analysis revealed sexually dimorphic neuroprotective mechanisms: oxidative stress protection pathways in females and membrane stability/reduced neuronal excitability markers in males.
Corrigan, Rachel R; Labrador, Luis; Grizzanti, John; Mey, Megan; Piontkivska, Helen; Casadesús, Gemma ·
RPEP-06814 · 2023The novel 28-amino-acid peptide Δ-TRTX-AC1, isolated from Aphonopelma chalcodes tarantula venom, demonstrated multiple beneficial effects: it evoked glucose-dependent insulin secretion from beta cells via KATP and calcium channel signaling pathways, enhanced beta-cell proliferation, and provided significant protection against cytokine-induced apoptosis.
In C57BL/6 mice at 250 nmol/kg, Δ-TRTX-AC1 decreased blood glucose levels and produced a significant satiating effect. While it did not enhance exenatide's glucose-lowering effects, it significantly augmented exenatide-mediated appetite suppression, suggesting complementary mechanisms of action. The peptide adopted a characteristic inhibitor cysteine knot (ICK) structure and was non-toxic to beta cells.
Coulter-Parkhill, A; Dobbin, Swm; Tanday, N; Gault, V A; McClean, S; Irwin, N ·
RPEP-06820 · 2023Two novel peptides, IIPNEVY and ITPPVMLPP, were identified from green coffee bean protein hydrolysates with ACE inhibitory IC50 values of 57.54 and 40.37 μM, respectively. Molecular docking revealed both peptides bind near the S1 active pocket of ACE to form stable enzyme-peptide complexes.
The peptides work through different inhibition mechanisms: IIPNEVY acts as a noncompetitive inhibitor (binding to the enzyme at a site separate from the substrate), while ITPPVMLPP is a mixed-type inhibitor (can bind both the free enzyme and the enzyme-substrate complex). Five candidate peptides were initially identified through in silico screening, with these two showing the strongest activity in vitro.
Dai, Haopeng; He, Min; Hu, Guilin; Li, Zhongrong; Al-Romaima, Abdulbaset; Wu, Zhouwei; Liu, Xiaocui; Qiu, Minghua ·
RPEP-06821 · 2023Using site-directed mutagenesis, researchers identified specific amino acid residues in the GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR) that are critical for activation by multi-target peptide agonists. Three dual agonists (peptide 15, MEDI0382, and SAR425899) and one triple agonist (peptide 20) were compared to the natural hormones GLP-1 and glucagon across two signaling pathways — cAMP accumulation and ERK1/2 phosphorylation.
The results revealed distinct residue networks that control how each multi-target agonist activates these receptors, and showed that the signaling patterns differ significantly between the agonists. This means each dual/triple agonist has its own unique 'fingerprint' of receptor activation, which could be exploited to design drugs with optimized therapeutic profiles and reduced side effects.
Darbalaei, Sanaz; Chang, Ru-Lue; Zhou, Qing-Tong; Chen, Yan; Dai, An-Tao; Wang, Ming-Wei; Yang, De-Hua · In Vitro
RPEP-06822 · 2023The H-NP-YARA system (chitosan hydrogel with YARA-loaded pNIPAM nanoparticles) demonstrated:
- Loading efficiency: >50% for YARA peptide in nanoparticles
- Sustained release: up to 120 hours from both nanoparticles and hydrogels
- Skin penetration: 2-fold (NP alone) and 4-fold (hydrogel-NP) more YARA delivered into viable skin layers vs. free peptide at 12 hours, in both intact and impaired barrier conditions
- In vitro inflammation: NP-YARA and H-NP-YARA reduced inflammatory cytokines up to 20-fold compared to untreated inflamed human keratinocytes
- Ex vivo skin model: NP-YARA reduced IL-1β, IL-6, and TNF-α up to 3.3-fold; H-NP-YARA reduced them up to 17-fold compared to drug in solution
- Hydrogel maintained porous structure after nanoparticle incorporation (SEM confirmed)
Dartora, Vanessa F C; Passos, Julia Sapienza; Osorio, Blanca; Hung, Ruei-Chun; Nguyen, Michael; Wang, Aijun; Panitch, Alyssa ·
RPEP-06825 · 2023Across SURPASS 1–5 trials, tirzepatide (5, 10, 15 mg weekly) produced HbA1c reductions of 1.87–2.59% (20–28 mmol/mol) and body weight reductions of 6.2–12.9 kg. In SURPASS-2, tirzepatide exceeded semaglutide 1 mg on both glycemic and weight outcomes. Additional cardiometabolic benefits included reductions in blood pressure, visceral adiposity, and triglycerides. Safety was similar to the GLP-1 receptor agonist class with low hypoglycemia risk when used without insulin.
De Block, Christophe; Bailey, Clifford; Wysham, Carol; Hemmingway, Andrea; Allen, Sheryl Elaine; Peleshok, Jennifer ·
RPEP-06829 · 2023Across 6 RCTs with 4,036 participants (12-72 weeks):
**Weight loss vs placebo:**
- Tirzepatide 5 mg: -7.7 kg (-8.1%)
- Tirzepatide 10 mg: -11.6 kg (-11.9%)
- Tirzepatide 15 mg: -11.8 kg (-12.4%)
- All doses: p<0.001
Tirzepatide also significantly reduced BMI and waist circumference.
**Side effects at 15 mg vs placebo:**
- Nausea: OR 4.2 (4.2× more likely)
- Vomiting: OR 7.0 (7× more likely)
- Diarrhea: OR 2.8 (2.8× more likely)
All three doses showed a clear dose-response relationship for both efficacy and side effects.
de Mesquita, Yasmin Luz Lima; Pera Calvi, Izabela; Reis Marques, Isabela; Almeida Cruz, Sara; Padrao, Eduardo Messias Hirano; Carvalho, Pedro Emanuel de Paula; da Silva, Caroliny Hellen Azevedo; Cardoso, Rhanderson; Moura, Filipe Azevedo; Rafalskiy, Vladimir Vitalievich ·
RPEP-06837 · 2023PF-6870961, the major hydroxy metabolite of the ghrelin receptor inverse agonist PF-5190457, demonstrated its own binding affinity and inverse agonist activity at GHSR1a. While it had lower binding affinity and potency for blocking inositol phosphate accumulation compared to the parent compound, it showed increased inhibitory potency at β-arrestin recruitment — a form of biased inverse agonism. Intraperitoneal injection suppressed food intake in both male and female rats under food-restricted and ad libitum conditions. Knockout experiments confirmed these effects were mediated specifically through the ghrelin receptor.
Deschaine, Sara L; Hedegaard, Morten A; Pince, Claire L; Farokhnia, Mehdi; Moose, Jacob E; Stock, Ingrid A; Adusumalli, Sravani; Akhlaghi, Fatemeh; Hougland, James L; Sulima, Agnieszka; Rice, Kenner C; Koob, George F; Vendruscolo, Leandro F; Holst, Birgitte; Leggio, Lorenzo ·
RPEP-06840 · 2023All three cell-penetrating peptides — penetratin, shuffle, and penetramax — adsorbed to lipid bilayer surfaces and induced liposome clustering at specific peptide-to-lipid ratios. However, the nature of their interactions differed significantly: penetratin caused irreversible clustering, penetramax caused partly reversible clustering, and shuffle caused fully reversible clustering.
Shuffle and penetramax additionally caused liposome shape deformation, while penetratin did not. Importantly, none of the peptides disrupted liposome integrity under any tested conditions, meaning they interact with membranes without destroying them — a critical requirement for safe drug delivery applications.
Diedrichsen, Ragna Guldsmed; Vetri, Valeria; Prévost, Sylvain; Foderà, Vito; Nielsen, Hanne Mørck ·
RPEP-06842 · 2023Significant decreases in neuropeptide Y (p = 0.02) and neurokinin A (p = 0.03) were observed.
Dionysakopoulou, Christina; Lianou, Loukia; Boutopoulou, Barbara; Giannakopoulou, Margarita; Vlachioti, Efrosini; Koumpagioti, Despoina; Bozas, Evangelos; Matziou, Vasiliki ·
RPEP-06844 · 2023In a phase 2 clinical trial, retatrutide — the first triple-agonist peptide targeting GLP-1, GIP, and glucagon receptors simultaneously — produced dose-dependent weight loss ranging from 7.2% to approximately 18% over just 24 weeks. These results are remarkable given the short study duration, suggesting even greater weight loss with longer treatment. The most common side effects were gastrointestinal (nausea, diarrhea, vomiting), consistent with GLP-1 receptor agonism.
The author notes a concern: retatrutide increased heart rate by up to 6.7 beats per minute, which may partially offset the cardiovascular benefits of weight loss. Critically, no head-to-head comparator trials against semaglutide or tirzepatide are ongoing, which the author views as a significant gap in the drug's development.
Doggrell, Sheila A · Review
RPEP-06845 · 2023Six peptides were identified from hydrolyzed loach protein: D-1 (SERDPSNIKWGDAGAQ), D-2 (TVDGPSGKLWR), D-3 (NDHFVKL), D-4 (AFRVPTP), D-5 (DAGAGIAL), and D-6 (VSVVDLTVR). All showed antioxidant activity, with the <3 kDa fraction exhibiting the strongest DPPH, hydroxyl radical, and superoxide radical scavenging ability.
Peptide D-4 showed ACE inhibitory activity with an IC50 of 95.07 μg/mL (0.12 mM), and D-2 also inhibited ACE. For cholesterol reduction, D-2 inhibited pancreatic cholesterol esterase (IC50 3.19 mg/mL, 2.62 mM), with D-3 and D-6 also showing CE inhibitory activity. Molecular docking confirmed these peptides bind to key amino acids in the catalytic domains of both enzymes.
Dou, Baojie; Wu, Xudong; Xia, Zihan; Wu, Guanghao; Guo, Quanyou; Lyu, Mingsheng; Wang, Shujun ·
RPEP-06847 · 2023The researchers created polyplexes (polymer-siRNA complexes) using a newly designed copolymer (PHEA-bAPAE-PEG-MLB) and decorated their surface with thiolated TAT peptide via thiol-ene chemistry. The TAT-decorated polyplexes demonstrated several key properties:
They maintained siRNA binding during mucus diffusion, passed through the mucin layer efficiently despite only forming weak bonds with mucin chains, and were highly cytocompatible (non-toxic to cells). In cellular uptake studies, the polyplexes effectively penetrated into the cytoplasm of bronchial epithelial cells and reduced IL-8 gene expression after LPS-induced inflammation. The final formulation was converted into an inhalable dry powder by encapsulating the polyplexes in mannitol-based microparticles via spray freeze drying, producing highly porous particles with suitable aerodynamic properties for lung delivery.
Drago, Salvatore Emanuele; Cabibbo, Marta; Craparo, Emanuela Fabiola; Cavallaro, Gennara ·
RPEP-06853 · 2023Key results for liposome-delivered GHK-Cu:
- Stable liposomes of approximately 100 nm were produced using both anionic (AL) and cationic (CL) hydrogenated lecithin
- Cationic liposomes at 25 mg/cm³ hydrated with 0.5 mg/cm³ GHK-Cu achieved the best encapsulation efficiency: 31.7 ± 0.9%
- Anionic liposomes achieved 20.0 ± 2.8% encapsulation
- Cationic liposomes had higher bilayer fluidity
- GHK-Cu inhibited elastase activity by 48.90 ± 2.50%
- GHK-Cu did not significantly affect tyrosinase activity
- The 49% elastase inhibition supports skin structural integrity by reducing elastin degradation
Dymek, Michał; Olechowska, Karolina; Hąc-Wydro, Katarzyna; Sikora, Elżbieta ·
RPEP-06854 · 2023Researchers created three new peptide hydrogel materials by combining the self-assembling RADA16-I scaffold with biologically active wound-healing peptide motifs (GHK, KGHK, and RDKVYR) connected through an enzyme-cleavable linker (AAPV). The design is smart: when wound-related enzymes (neutrophil elastase) encounter the hydrogel, they cut the linker and release the active healing peptides at the wound site.
The hybrid materials maintained the same gelling properties as the original RADA16-I scaffold, showed no toxicity to skin cells, and promoted better cell growth than the unmodified gel. In mice with dorsal skin wounds, topical application of RADA-GHK and RADA-KGHK hydrogels improved wound healing as confirmed by histological analysis.
Dzierżyńska, Maria; Sawicka, Justyna; Deptuła, Milena; Sosnowski, Paweł; Sass, Piotr; Peplińska, Barbara; Pietralik-Molińska, Zuzanna; Fularczyk, Martyna; Kasprzykowski, Franciszek; Zieliński, Jacek; Kozak, Maciej; Sachadyn, Paweł; Pikuła, Michał; Rodziewicz-Motowidło, Sylwia · Animal Study
RPEP-06856 · 2023Spirulina protein hydrolysate (SPH)-loaded nanoliposomes (NLPs) were successfully created with a particle size of 158 nm and zeta potential of -48 mV, indicating good stability. Key findings:
**In vitro**: SPH showed no toxicity to human fibroblast cells (HFFF-2) and actually increased cell growth. Scratch wound assays confirmed faster cell migration with SPH treatment.
**In vivo (162 mice, 9 groups)**: The SPH-NLP treated group showed superior results compared to blank gel, blank NLPs, and free SPH groups at all concentrations (2.5%, 5%, 10%):
- Higher wound contraction rates
- Increased epithelialization
- Greater fibroblast proliferation
- Elevated expression of bFGF (growth factor), CD31 (blood vessel marker), and COL1A (collagen)
The nanoliposome encapsulation enhanced peptide delivery and efficacy beyond free peptide application.
Ebrahimi, Alireza; Reza Farahpour, Mohammad; Amjadi, Sajed; Mohammadi, Maryam; Hamishehkar, Hamed ·
RPEP-06858 · 2023Applying Sandalore® (a synthetic sandalwood-scented compound) to organ-cultured human skin activated an olfactory receptor (OR2AT4) in epidermal cells, causing them to produce and secrete more dermcidin — an antimicrobial peptide. This was the first demonstration that epidermal keratinocytes can produce dermcidin (previously thought to come only from sweat glands). LL-37 (cathelicidin) expression was not affected.
The dermcidin-enriched culture medium selectively inhibited Staphylococcus aureus growth while promoting the growth of beneficial skin bacteria (S. epidermidis) and the commensal fungus Malassezia restricta. This suggests Sandalore® could reshape the skin microbiome by boosting the skin's natural antimicrobial defenses.
Edelkamp, Janin; Lousada, Marta B; Pinto, Daniela; Chéret, Jérémy; O'Sullivan, James D B; Biundo, Antonio; Jimenez, Francisco; Funk, Wolfgang; Roessing, Christian; Rippmann, Volker; Paus, Ralf; Bertolini, Marta · Ex Vivo
RPEP-06860 · 2023Systematic engineering of a human lactoferrin-derived CPP revealed that amphipathic sequence motifs are the critical structural determinant for cytosolic mRNA delivery.
Neither histidine incorporation (to promote the proton sponge effect for endosomal escape), nor arginine-to-lysine/ornithine substitutions, nor disulfide-mediated oligomerization were sufficient to convert an uptake-only CPP into a delivery-active one — despite all modified peptides showing cellular uptake. Only the transfer of amphipathic motifs from the delivery-active PepFect14 achieved functional mRNA delivery, with some additional benefit from oligomerization.
Egberink, Rik Oude; van Asbeck, Alexander H; Boswinkel, Milou; Muradjan, Grigor; Dieker, Jürgen; Brock, Roland ·
RPEP-06863 · 2023In 96 humanized mice with gastroenteropancreatic NETs, the early PRRT group (PRRT on day 0 followed by anti-PD1 on day 3) showed the most significant tumor reduction: 205 mm³ to 78 mm³ over 21 days (p=0.0074). PET/MRI imaging confirmed the strongest T-cell activation in this group, with SUVmax increasing from 0.73 to 3.36 (p<0.05) for granzyme-B uptake — indicating robust cytotoxic T-cell activation. The simultaneous and anti-PD1-first groups showed less tumor growth reduction, and PRRT or anti-PD1 alone were least effective.
Esfahani, Shadi A; De Aguiar Ferreira, Carolina; Summer, Priska; Mahmood, Umar; Heidari, Pedram ·
RPEP-06866 · 2023Lupin protein treated with ultrasound and then enzymatically hydrolyzed produced peptide mixtures with ACE-inhibitory activity. The unfractionated alcalase hydrolysate (IC50 = 3.21 mg/mL) and flavourzyme hydrolysate (IC50 = 3.32 mg/mL) were more potent than their ultrafiltrated fractions (IC50 = 6.09–7.45 mg/mL), suggesting synergistic effects among peptides.
Molecular docking analysis identified six novel peptides as predicted ACE inhibitors: AIPPGIPY, SVPGCT, and QGAGG from the alcalase hydrolysate, and AIPINNPGKL, SGNQGP, and PPGIP from the flavourzyme hydrolysate.
Fadimu, Gbemisola J; Gan, Chee-Yuen; Olalere, Olusegun A; Farahnaky, Asgar; Gill, Harsharn; Truong, Tuyen ·
RPEP-06868 · 2023The functional self-assembling peptide (F-SAP) and silk fibroin (SF) cooperatively assembled into a hybrid nanofiber hydrogel through a mechanism driven by osmotic pressure and electrostatic interactions. SF micelles diffused into the F-SAP solution and rearranged into rod-like filaments oriented nearly perpendicular to the peptide nanofibers. Spectroscopy confirmed that SF underwent a structural transition from random coil to β-sheet, which strengthened the gel mechanically.
When combined with controlled release of NT-3 (neurotrophin-3), the hybrid gel created a permissive environment for neural regeneration: it provided nanofiber substrates for axon growth, modulated inflammation, and promoted remyelination. This resulted in measurable improvements in locomotion and electrophysiological function. The hydrogel demonstrated potential as a long-term in vivo stent for spinal cord injury treatment.
Feng, Feng; Song, Xiyong; Tan, Zan; Tu, Yujie; Xiao, Longyou; Xie, Pengfei; Ma, Yahao; Sun, Xiumin; Ma, Junwu; Rong, Limin; He, Liumin ·