RPEP-05932 · 2021Virus-mimicking mesoporous silica nanoparticles coated with the cell-penetrating peptide KLPVM and glutaric anhydride achieved near-neutral surface charge (ζ-potential -0.49 mV), enabling them to penetrate the intestinal mucus layer without binding to mucin — unlike positively charged nanoparticles (ζ-potential +35.00 mV). Transepithelial transport was 2.4-fold higher than unmodified nanoparticles. In diabetic rats, insulin loaded into these nanoparticles reduced blood glucose by nearly 50%, with 2.1-fold higher bioavailability than insulin administered directly into the jejunum. No significant toxicity was observed in preliminary in vitro or in vivo studies.
Zhang, Yi; Xiong, Mengting; Ni, Xiaomin; Wang, Jingrou; Rong, Hehui; Su, Yuqing; Yu, Shihui; Mohammad, Imran Shair; Leung, Sharon Shui Yee; Hu, Haiyan ·
RPEP-05958 · 2022The gastric auto-injector capsule achieved remarkable drug delivery performance in swine:
• Up to 80% absolute bioavailability — meaning 80% of the drug reached the bloodstream, comparable to injection
• Maximum plasma concentration reached within 30 minutes of oral dosing
• Capable of delivering up to 4 mg doses per capsule
• Performance was 10× better than previous injector capsule designs and up to 100× better than chemical permeation enhancement technologies
• Successfully delivered four different drug classes: adalimumab (monoclonal antibody), a GLP-1 analog (peptide), recombinant human insulin (peptide), and epinephrine (small molecule)
• Multi-day dosing experiments in awake animals demonstrated consistent performance and translational potential
Abramson, Alex; Frederiksen, Morten Revsgaard; Vegge, Andreas; Jensen, Brian; Poulsen, Mette; Mouridsen, Brian; Jespersen, Mikkel Oliver; Kirk, Rikke Kaae; Windum, Jesper; Hubálek, František; Water, Jorrit J; Fels, Johannes; Gunnarsson, Stefán B; Bohr, Adam; Straarup, Ellen Marie; Ley, Mikkel Wennemoes Hvitfeld; Lu, Xiaoya; Wainer, Jacob; Collins, Joy; Tamang, Siddartha; Ishida, Keiko; Hayward, Alison; Herskind, Peter; Buckley, Stephen T; Roxhed, Niclas; Langer, Robert; Rahbek, Ulrik; Traverso, Giovanni ·
RPEP-05968 · 2022Kef-1 peptide reduced ROS production and improved vascular structure in 2K1C mice.
Aires, Rafaela; Gobbi Amorim, Fernanda; Côco, Larissa Zambom; da Conceição, Amanda Pompermayer; Zanardo, Tadeu Ériton Caliman; Taufner, Gabriel Henrique; Nogueira, Breno Valentim; Vasquez, Elisardo Corral; Melo Costa Pereira, Thiago; Campagnaro, Bianca Prandi; Dos Santos Meyrelles, Silvana ·
RPEP-05973 · 2022Nose-to-brain (N-to-B) delivery offers a non-invasive way to get peptide drugs into the brain by bypassing the blood-brain barrier entirely. The olfactory and trigeminal nerves provide direct pathways from the nasal cavity to the brain, allowing peptide drugs to reach the CNS without needing injections or having to survive the digestive system. This approach can rapidly target the brain while minimizing systemic exposure and side effects. The review covers clinical applications, nasal delivery devices, and the current limitations of this approach.
Alabsi, Wafaa; Eedara, Basanth Babu; Encinas-Basurto, David; Polt, Robin; Mansour, Heidi M · Review
RPEP-05975 · 2022Two patients with migraine with aura reported striking improvements in their aura symptoms while taking anti-CGRP antibodies. One patient on galcanezumab experienced complete disappearance of aura, while another on erenumab had reduced aura duration and intensity. This is notable because anti-CGRP antibodies are primarily expected to work peripherally (they can't easily cross the blood-brain barrier), yet migraine aura is believed to originate from cortical spreading depression — a brain phenomenon.
Albanese, Maria; Mercuri, Nicola Biagio ·
RPEP-05981 · 2022β-caryophyllene (100 mg/day for 8 weeks) significantly reduced Yale Food Addiction Scale scores compared to placebo (change: 1.5 ± 0.9 vs. −0.7 ± 1.4; corrected p=0.05).
Serum orexin-A levels significantly decreased within the β-caryophyllene group (p=0.02), though the between-group comparison did not reach significance after correction (p=0.09). No significant effects were observed on body composition, anthropometric indices, appetite, eating behavior, dietary intake, physical activity, mental health (stress, anxiety, depression), or levels of oxytocin and neuropeptide Y (NPY).
Alizadeh, Shahab; Djafarian, Kurosh; Mofidi Nejad, Maryam; Yekaninejad, Mir Saeed; Javanbakht, Mohammad Hassan ·
RPEP-05983 · 2022Using STC-1 enteroendocrine cells after in vitro digestion:
• GLP-1 release: Spelt milk was highest (910.17 pg/ml), followed closely by cow's milk (876.59 pg/ml), with no significant difference between them
• CCK release: Cow's milk stimulated significantly more CCK than plant milks overall. Among plant alternatives, tiger nut milk was highest (228.96 pg/ml), followed by hazelnut milk (220.04 pg/ml)
• Antioxidant capacity: Total phenolic content increased after digestion for all samples. Soymilk had the highest antioxidant values (ORAC: 25.41 µmol TE/ml)
• Cow's milk and soymilk had the highest post-digestion total phenolic content (165.76 and 153.71 mg GAE/100 ml)
Aly, Esmat; Sánchez-Moya, Teresa; Darwish, Aliaa A; Ros-Berruezo, Gaspar; López-Nicolás, Rubén ·
RPEP-05991 · 2022Retro-inverso (RI) type inhibitors of HTLV-1 protease containing a hydroxyethylamine dipeptide isostere were synthesized with different isoleucine side-chain configurations. Replacing D-Ile with D-allo-Ile in the corresponding substrate positions produced more potent inhibitors.
The results demonstrated that mimicking the complete topology of the parent inhibitor — both backbone and side-chain spatial arrangements — is critical for designing effective retro-inverso protease inhibitors. Simply reversing the backbone without matching side-chain configurations leads to suboptimal binding.
Awahara, Chiyuki; Oku, Daiki; Furuta, Saki; Kobayashi, Kazuya; Teruya, Kenta; Akaji, Kenichi; Hattori, Yasunao ·
RPEP-05997 · 2022The researchers identified immunogenic peptides from six common codon 12 RAS mutations (G12A, G12C, G12D, G12R, G12S, and G12V) that bind to HLA-A*02:01 and HLA-A*03:01, the two most common HLA types. These peptides elicited strong CD8+ T cell responses.
Modifying the anchor residues of these peptides enhanced their binding affinity to HLA-A*02:01, and the resulting T cells responded to both the modified and original peptide forms. Crucially, cytotoxic T cells generated against these peptides specifically lysed tumor cells expressing mutant RAS. In humanized HLA-A2/DR1 mice, vaccination with a long peptide containing an anchor-modified G12V epitope generated CD8+ T cells that recognized both the original peptide and a human cancer cell line harboring the G12V mutation.
Baleeiro, Renato B; Dunmall, Louisa S Chard; Liu, Peng; Lu, Shuangshuang; Lone, Yuchun; Lemoine, Nicholas R; Wang, Yaohe ·
RPEP-06001 · 2022BPC-157 at doses of 10 ng/kg and 10 µg/kg (given intraperitoneally either 30 min before or 5 min after isoprenaline) significantly reduced all necrosis markers: CK, CK-MB, LDH, and cardiac troponin T. Treated rats showed no visible infarcted area on gross examination, attenuated histological damage, no ST-T ischemic changes on ECG, and preservation of systolic left ventricular function on echocardiography.
BPC-157 also counteracted the early multi-organ failure seen at 30 min post-isoprenaline (brain, heart, lung, liver, kidney, and GI lesions), reduced thrombosis, and normalized vascular pressures (intracranial, portal, caval hypertension and aortal hypotension) via activation of the azygos vein. The protective effects involved reduced oxidative stress and maintained NO system function through interaction with eNOS and COX2 gene expression.
Barisic, Ivan; Balenovic, Diana; Udovicic, Mario; Bardak, Darija; Strinic, Dean; Vlainić, Josipa; Vranes, Hrvoje; Smoday, Ivan Maria; Krezic, Ivan; Milavic, Marija; Sikiric, Suncana; Uzun, Sandra; Zivanovic Posilovic, Gordana; Strbe, Sanja; Vukoja, Ivan; Lovric, Eva; Lozic, Marin; Sever, Marko; Lovric Bencic, Martina; Boban Blagaic, Alenka; Skrtic, Anita; Seiwerth, Sven; Sikiric, Predrag ·
RPEP-06004 · 2022DNAJB1-PRKACA fusion-derived peptides were confirmed as genuine HLA-presented neoantigens on tumor cells by mass spectrometry-based immunopeptidome analysis. These peptides induced both cytotoxic CD8+ T cells and T-helper 1 CD4+ T cells in preclinical testing. Single-cell RNA sequencing identified multiple T cell receptors specific for the fusion neoepitopes.
In a single-patient clinical application, vaccination with DNAJB1-PRKACA-derived peptides (combined with ongoing PARP inhibitor therapy) induced multifunctional CD4+ T cells with activated Th1 phenotype and high T cell receptor clonality. The vaccine-induced immune responses persisted over time and were accompanied by durable relapse-free survival of more than 21 months — in striking contrast to the patient's previous pattern of recurrent short-interval relapses under various treatments.
Bauer, Jens; Köhler, Natalie; Maringer, Yacine; Bucher, Philip; Bilich, Tatjana; Zwick, Melissa; Dicks, Severin; Nelde, Annika; Dubbelaar, Marissa; Scheid, Jonas; Wacker, Marcel; Heitmann, Jonas S; Schroeder, Sarah; Rieth, Jonas; Denk, Monika; Richter, Marion; Klein, Reinhild; Bonzheim, Irina; Luibrand, Julia; Holzer, Ursula; Ebinger, Martin; Brecht, Ines B; Bitzer, Michael; Boerries, Melanie; Feucht, Judith; Salih, Helmut R; Rammensee, Hans-Georg; Hailfinger, Stephan; Walz, Juliane S ·
RPEP-06005 · 2022Vaccines containing the native (unmodified) Melan-A/MART-1 tumor peptide generated CD8 T cells with better functionality and superior cross-reactivity against potential low-affinity escape variants, compared to T cells induced by vaccines with an HLA affinity-optimized peptide.
Using affinity-optimized NY-ESO-1-specific T cell receptors, the researchers found that peptide:HLA affinity and TCR-peptide:HLA affinity both have profound and distinct effects on T cell responses, with additive contributions and no hierarchical dominance of one parameter over the other. T cells from tumor-infiltrated lymph nodes showed heterogeneous, clonotype-dependent functional profiles.
Baumgaertner, Petra; Schmidt, Julien; Costa-Nunes, Carla-Marisa; Bordry, Natacha; Guillaume, Philippe; Luescher, Immanuel; Speiser, Daniel E; Rufer, Nathalie; Hebeisen, Michael ·
RPEP-06006 · 2022C9 selectively inhibited MRGPRX2-mediated mast cell degranulation with an IC50 of approximately 300 nM. Key specifics:
• C9 blocked degranulation in response to substance P, PAMP-12 (a pro-adrenomedullin peptide), and rocuronium in cells expressing MRGPRX2
• C9 did NOT inhibit mast cell activation through FcεRI (IgE receptor) or the anaphylatoxin C3a — demonstrating high selectivity for MRGPRX2
• C9 also blocked β-arrestin recruitment and receptor internalization, inhibiting both major signaling arms of MRGPRX2
• An inactive analog (C7) had no effect, confirming the specificity of C9's action
• A naturally occurring MRGPRX2 variant (V282M) that shows constitutive β-arrestin activity was also significantly inhibited by C9
• C9 did not block the mouse ortholog MrgprB2, indicating species specificity
Bawazir, Maram; Amponnawarat, Aetas; Hui, Yvonne; Oskeritzian, Carole A; Ali, Hydar ·
RPEP-06015 · 2022The review synthesizes evidence showing that the oxytocin system influences social behavior through multiple pathways — direct intranasal administration, genetic variation in oxytocin-related genes, and epigenetic modifications. The contrasting social phenotypes of autism spectrum disorder (social difficulties) and Williams syndrome (excessive sociability) provide a natural experiment for understanding the oxytocinergic system.
The authors conclude that inconsistencies in oxytocin research stem largely from methodological issues: problems with measuring central oxytocin levels, variable intranasal administration protocols, and failure to account for individual differences in the oxytocin system that determine treatment response.
Boulton, Kelsie A; Guastella, Adam J ·
RPEP-06032 · 2022Cell-penetrating peptides conjugated with organelle-targeting sequences represent an advancing strategy for intracellular drug delivery. The review summarizes how CPPs can be engineered to deliver cargo to specific subcellular compartments including mitochondria, nuclei, endoplasmic reticulum, and lysosomes. This organelle-level targeting moves drug delivery beyond tissue-level or cell-level precision, improving therapeutic efficacy while reducing off-target toxicity and potentially overcoming drug resistance mechanisms.
Cerrato, Carmine Pasquale; Langel, Ülo ·
RPEP-06036 · 2022The prediction pipeline selected 278 neoepitopes from tumor tissues of 46 patients with hepatocellular carcinoma or colorectal carcinoma metastases. Validation in HLA-A2, A24, B35, and B07 transgenic mice using ELISpot and killing assays demonstrated that the algorithm predicted immunogenic neopeptides with an area under the curve of 0.687 (p<0.0001).
Importantly, the study showed that short predicted neopeptides are intrinsically present in tumor cells as natural cleavage products of longer peptides, confirming biological relevance. Long peptides containing the predicted neoepitopes also successfully induced cytotoxic T lymphocyte (CTL) responses.
Charneau, Jimmy; Suzuki, Toshihiro; Shimomura, Manami; Fujinami, Norihiro; Mishima, Yuji; Hiranuka, Kazushi; Watanabe, Noriko; Yamada, Takashi; Nakamura, Norihiro; Nakatsura, Tetsuya ·
RPEP-06040 · 2022The neoantigen peptide vaccine (NeoVAC) combined with anti-PD-1 immunotherapy demonstrated:
- 80% durable tumor regression in orthotopic (liver-implanted) HCC mouse models
- Long-term immune memory against the tumor (indicating durable protection against recurrence)
- Dramatically increased CD8+ tissue-resident memory T cells (TRMs) in the tumor microenvironment
- CD8+ TRM infiltration positively correlated with treatment efficacy
- Strong tumor-killing capacity of CD8+ TRMs confirmed both in vitro and in vivo
- Validated in autologous patient-derived HCC cells (human cancer cells killed by TRMs)
The vaccine consisted of seven immunogenic neoantigen peptides with clinical-grade Poly(I:C) adjuvant. Single-cell RNA sequencing revealed the immune mechanisms underlying the synergistic effect.
Chen, Hengkai; Li, Zhenli; Qiu, Liman; Dong, Xiuqing; Chen, Geng; Shi, Yingjun; Cai, Linsheng; Liu, Wenhan; Ye, Honghao; Zhou, Yang; Ouyang, Jiahe; Cai, Zhixiong; Liu, Xiaolong ·
RPEP-06043 · 2022The optimized stapled peptide-PROTAC hybrid SPMI-HIF2-1 showed similar binding affinity for both MDM2 and MDMX compared to its linear counterpart, but with higher helical content, improved proteolytic stability, better cellular permeability, and improved pharmacokinetics. In subcutaneous and orthotopic colorectal cancer xenograft models, SPMI-HIF2-1 effectively killed cancer cells and inhibited tumor progression through simultaneous atypical degradation of both MDM2 and MDMX, leading to durable p53 activation. Structural analysis confirmed the molecule simultaneously bound the target protein and E3 ligase in a ternary complex.
Chen, Si; Li, Xiang; Li, Yinghua; Yuan, Xing; Geng, Chenchen; Gao, Songyan; Li, Jinyang; Ma, Bohan; Wang, Zhe; Lu, Wuyuan; Hu, Hong-Gang ·
RPEP-06048 · 2022Vincristine treatment (0.1 mg/kg/day i.p. for 14 days) significantly increased substance P expression by 30.3% ± 2.4% in the superficial layers of the rat spinal dorsal horn compared to saline controls, confirmed by both immunohistochemistry and direct measurement of substance P levels in spinal cord tissue.
The neurokinin 1 (NK1) receptor antagonist aprepitant (20 mg/kg, s.c.) significantly inhibited the mechanical allodynia and hyperalgesia caused by vincristine, demonstrating that substance P signaling through the NK1 receptor is a key mediator of this chemotherapy-induced neuropathic pain.
Chiba, Terumasa; Kambe, Toshie; Yamamoto, Ken; Kawakami, Kazuyoshi; Taguchi, Kyoji; Abe, Kenji ·
RPEP-06050 · 2022The peptide nanofiber-coated PLGA nanocomposites demonstrated dramatically enhanced cellular uptake: 3-fold higher delivery into primary lung epithelial cells and macrophages, and 10-fold higher delivery into endothelial cells compared to naked PLGA nanoparticles. Compared to nanoparticles modified with traditional monomeric cell-penetrating peptides, the nanofiber-coated version still showed 2-fold improvement.
Mechanistic studies indicated that the nanocomposites enter cells through mixed macropinocytosis and passive energy-independent mechanisms, with endosomal escape occurring within 24 hours. The composites also demonstrated potent mucus permeation. The formulation survived freeze-drying and nebulization without losing physicochemical or biological activity, supporting translational potential as an inhaled therapeutic system.
Chintapula, Uday; Yang, Su; Nguyen, Trinh; Li, Yang; Jaworski, Justyn; Dong, He; Nguyen, Kytai T ·
RPEP-06059 · 2022The review catalogs the challenges of endogenous opioid peptide research:
- Over 20 unique opioid peptides derived from 4 precursor molecules (proopiomelanocortin, proenkephalin, prodynorphin, pronociceptin)
- Low in vivo concentrations make detection difficult
- Complex processing and release dynamics complicate interpretation
- Traditional techniques (microdialysis, RIA, tissue-level measurements) have significant limitations for real-time behavioral studies
New techniques — including genetically encoded sensors, advanced mass spectrometry, and improved microdialysis methods — are beginning to overcome these barriers and enable direct measurement of specific opioid peptides during behavioral manipulations.
Conway, Sineadh M; Mikati, Marwa O; Al-Hasani, Ream ·
RPEP-06060 · 2022The central melanocortin system — a brain circuitry driven by POMC, AgRP, and neuropeptide Y peptides acting on melanocortin receptors — plays a dual role in regulating both feeding behavior and mood. This shared circuitry may explain why obesity and depression so often co-occur.
The review highlights that DSM-5 recognizes two depression subtypes with opposite metabolic profiles: melancholic depression (decreased appetite, weight loss) and atypical depression (hyperphagia, weight gain, fatigue). Melanocortin signaling appears to be involved in both patterns, suggesting it acts as a biological bridge between metabolic state and emotional regulation.
Copperi, Francesca; Kim, Jung Dae; Diano, Sabrina · Review
RPEP-06063 · 2022Amylin presents a pharmacological paradox in Alzheimer's disease research. On one hand, the pancreatic peptide self-aggregates into amyloid deposits — similar to amyloid-beta in AD brains — and has been implicated as a pathogenic factor in both type 2 diabetes and Alzheimer's. On the other hand, multiple studies show that amylin and its synthetic analog pramlintide (already FDA-approved for diabetes) have neuroprotective effects against Alzheimer's pathology.
This review argues that amylin receptor signaling in the central nervous system is far more complex than the simple "toxic aggregation" model suggests, and that pharmacological modulation of amylin receptors could be therapeutically beneficial for Alzheimer's — much as it already is for diabetes. The challenge is resolving how the same peptide can be both pathogenic and protective depending on context.
Corrigan, Rachel R; Piontkivska, Helen; Casadesus, Gemma · Review
RPEP-06064 · 2022Using genetic tools to manipulate specific neuron populations in mice, researchers showed that CCK-expressing neurons in the caudal brainstem are required for the full appetite-suppressing and body weight-lowering effects of the GLP-1 receptor agonist exendin-4. These same neurons also mediate conditioned taste avoidance — the animal model equivalent of nausea.
While these CCK neurons don't directly express GIP receptors, activating GIP receptors elsewhere reduced the recruitment of these GLP-1-responsive brainstem neurons. This resulted in a selective reduction of conditioned taste avoidance (nausea proxy) while preserving appetite suppression. The key neuroanatomical findings were confirmed in non-human primate brain tissue, supporting translational relevance.
Costa, Alessia; Ai, Minrong; Nunn, Nicolas; Culotta, Isabella; Hunter, Jenna; Boudjadja, Mehdi Boutagouga; Valencia-Torres, Lourdes; Aviello, Gabriella; Hodson, David J; Snider, Brandy M; Coskun, Tamer; Emmerson, Paul J; Luckman, Simon M; D'Agostino, Giuseppe · Animal Study
RPEP-06072 · 2022Among 15 synthesized derivatives of angiotensin (1-7), Ac-Ang (2-7)-NH2 emerged as the most promising: it is a good ACE inhibitor, resistant to enzymatic cleavage, and shows improved selectivity for the C-terminal domain (cACE) over the N-terminal domain (nACE). Molecular dynamics simulations identified key interactions — Val3 and Tyr4 with ACE subsites, particularly Val3's interaction with the S3 subsite — as critical for the peptide's selectivity. Removing Val3 greatly reduced peptide-enzyme interactions.
da Silva, Rogerio L; Papakyriakou, Athanasios; Carmona, Adriana K; Spyroulias, Georgios A; Sturrock, Edward D; Bersanetti, Patrícia A; Nakaie, Clovis R ·
RPEP-06082 · 2022Out of 136 patients, 88 (65%) had cranial autonomic symptoms (CAS). During 12 weeks of anti-CGRP treatment, the median reduction in monthly headache days was significantly greater in patients with CAS (-10, IQR -15 to -6) versus without CAS (-6, IQR -12 to -3; p=0.009). However, categorical response rates (30%, 50%, 75%, 100% reduction thresholds) did not differ significantly between groups. The findings suggest CAS may serve as a clinical biomarker of trigeminovascular activation that predicts better response to CGRP-targeting therapies.
De Matteis, Eleonora; Caponnetto, Valeria; Casalena, Alfonsina; Frattale, Ilaria; Gabriele, Amleto; Affaitati, Giannapia; Giamberardino, Maria Adele; Maddestra, Maurizio; Viola, Stefano; Pistoia, Francesca; Sacco, Simona; Ornello, Raffaele ·
RPEP-06085 · 2022Unimolecular dual and triple agonists targeting combinations of GLP-1, GIP, and glucagon receptors have demonstrated the ability to promote body weight loss, lower glucose levels, and reduce food intake in animal models of obesity. Multiple dual receptor agonists (GLP-1/GIP and GLP-1/glucagon combinations) are now in clinical development for obesity treatment.
The review highlights that glucagon may contribute to weight loss by reducing food intake, while simultaneous GLP-1 receptor activation helps maintain normal blood sugar control — addressing a key concern about using glucagon-based therapies in people with metabolic disorders.
Del Prato, Stefano; Gallwitz, Baptist; Holst, Jens Juul; Meier, Juris J ·
RPEP-06090 · 2022Polylactic acid films were modified with gallium ion implantation and functionalized with human beta-defensin-1 (hBD-1). Both components independently and synergistically reduced total live bacterial biomass on the surfaces.
A key novel finding was that defensin's antimicrobial activity was "unlocked" by surface immobilization — its in vitro effectiveness had previously been disappointing compared to its in vivo performance. Gallium implantation also reduced foreign body giant cell formation and IL-1β proinflammatory cytokine expression. The combined surfaces killed bacteria and reduced inflammation without inducing cellular toxicity.
Divakarla, Shiva Kamini; Das, Theerthankar; Chatterjee, Chandralekha; Ionescu, Mihail; Pastuovic, Zeljko; Jang, Jun-Hyeog; Al-Khoury, Hala; Loppnow, Harald; Yamaguchi, Seiji; Groth, Thomas; Chrzanowski, Wojciech ·
RPEP-06092 · 2022The study identified Mrgpra2a/b — previously orphan G-protein-coupled receptors on neutrophils — as the receptors for keratinocyte-derived defensins. This represents a novel epithelial-to-immune cell signaling axis.
Mice lacking either the entire defensin gene cluster in keratinocytes or the Mrgpra2a/b receptors developed skin dysbiosis characterized by reduced microbial diversity and expansion of Staphylococcus species. Both mutant lines showed impaired neutrophil abscess formation — a hallmark of antibacterial immunity — and increased susceptibility to S. aureus skin infections. Mechanistically, defensin activation of Mrgpra2 triggered neutrophil release of IL-1β and CXCL2, which are critical for amplifying and propagating the antibacterial immune response.
Dong, Xintong; Limjunyawong, Nathachit; Sypek, Elizabeth I; Wang, Gaofeng; Ortines, Roger V; Youn, Christine; Alphonse, Martin P; Dikeman, Dustin; Wang, Yu; Lay, Mark; Kothari, Ruchita; Vasavda, Chirag; Pundir, Priyanka; Goff, Loyal; Miller, Lloyd S; Lu, Wuyuan; Garza, Luis A; Kim, Brian S; Archer, Nathan K; Dong, Xinzhong ·
RPEP-06103 · 2022HNP-1 (human neutrophil protein 1), an alpha-defensin antimicrobial peptide, binds directly to the capsids of three different human adenovirus types (HAdV-C5, -D26, and -B35). This binding redirects the viruses to Toll-like receptor 4 (TLR4) on human phagocytes, leading to internalization of the virus-defensin complex.
The TLR4 engagement triggers an NLRP3 inflammasome response, resulting in the release of interleukin-1 beta (IL-1β) — a key inflammatory cytokine that activates broader immune responses. Notably, this IL-1β release occurred without significant disruption of the cell's plasma membrane, indicating a non-destructive, controlled activation pathway rather than cell death-associated inflammation.
Eichholz, Karsten; Tran, Tuan Hiep; Chéneau, Coraline; Tran, Thi Thu Phuong; Paris, Océane; Pugniere, Martine; Kremer, Eric J ·
RPEP-06104 · 2022In 60 diabetic rats, both dulaglutide and metformin significantly decreased blood pressure, blood glucose, serum lipids, and improved kidney functional parameters compared to untreated diabetic controls. These improvements were associated with increased antioxidant markers, decreased inflammatory markers (NF-κB gene expression), and reduced fibrotic changes in kidney tissue.
Adding cilostazol to either dulaglutide or metformin further enhanced some antioxidant and anti-inflammatory properties. Histopathological examination confirmed that treated groups had improved kidney tissue architecture compared to untreated diabetic rats. Dulaglutide also increased eNOS gene expression in kidney tissue, suggesting improved vascular function.
El Amin Ali, Amani M; Osman, Hamed M; Zaki, Azaa M; Shaker, Olfat; Elsayed, Asma Mohammed; Abdelwahed, Mostafa Yehia; Mohammed, Rahab Ahmed ·
RPEP-06107 · 2022Serum alpha-defensin levels were significantly elevated in type 2 diabetes patients both with diabetic neuropathy (n=47) and without complications (n=19) compared to healthy controls (n=19).
Alpha-defensin levels showed significant positive correlations with advanced glycation end products (AGEs), fasting blood glucose, and body mass index. The correlation with AGEs is particularly notable, as it suggests a crosstalk between innate immune antimicrobial peptides and the glycation pathway that may amplify chronic inflammation in diabetes.
El-Mowafy, Mohammed; Elgaml, Abdelaziz; Abass, Naglaa; Mousa, Amany A; Amin, Mohamed N ·
RPEP-06122 · 2022After 26 weeks, iGlarLixi produced a 35% median increase in beta-cell glucose sensitivity compared to GLP-1RA alone (p=0.0032). HbA1c decreased significantly more with iGlarLixi than with GLP-1RA alone (p<0.0001).
Notably, iGlarLixi reduced both fasting and stimulated insulin secretion (both p<0.0001 vs. GLP-1RA), indicating that the beta cells were being spared from overproduction while functioning more efficiently. The incremental meal tolerance test glucose area also showed a larger reduction with iGlarLixi (p<0.0001). Body weight increased modestly in the iGlarLixi group (+1.7 kg, p<0.0001). In the GLP-1RA-only group, despite weight loss and HbA1c improvement, no beta-cell function parameters changed significantly.
Ferrannini, Ele; Niemoeller, Elisabeth; Dex, Terry; Servera, Soraly; Mari, Andrea ·
RPEP-06123 · 2022The review consolidates evidence from six major cardiovascular outcome trials:
- Five human GLP-1-based and one exendin-based GLP-1RA reduced atherosclerotic cardiovascular events in T2DM patients at high cardiovascular risk
- Meta-analysis showed reduction in major adverse cardiovascular events (MACE) and all-cause mortality versus placebo
- Benefits were consistent regardless of structural homology (exendin-based vs. human GLP-1-based)
- Additional benefits: prevention of macroalbuminuria onset (kidney protection), blood pressure reduction, significant weight loss
- Safety: low hypoglycemia risk, no increase in pancreatitis events
- Cardiovascular benefits appear independent of glycemic control, suggesting direct protective mechanisms
Ferrari, Filipe; Scheffel, Rafael S; Martins, Vítor M; Santos, Raul D; Stein, Ricardo ·
RPEP-06124 · 2022A catalyst-free fluorobenzene stapling method was developed for cysteine-containing peptides that enables fine-tuning of macrocyclic peptide structure by selecting different regioisomers (ortho, meta, or para) of the fluorobenzene linker. When applied to melanocortin receptor agonists, the method generated a library of potent macrocyclic ligands from the same linear precursor, with small but significant differences in potency and efficacy depending on the staple geometry. NMR and circular dichroism confirmed that different stapling configurations tune the peptide's secondary structure.
Fischer, Niklas H; Fumi, Erik; Oliveira, Maria Teresa; Thulstrup, Peter W; Diness, Frederik ·
RPEP-06129 · 2022Substance P reduced expression of the tight junction protein occludin in human brain endothelial cells, but only when cells were at low confluence — at full confluence, no effect was observed. SP acted exclusively through a truncated form of the NK-1 receptor and stimulated Erk2 phosphorylation without triggering inflammatory cytokines (IL-6, IL-8) or ICAM-1. SP also restored nitric oxide production in cells exposed to TNF-α. Importantly, SP did not trigger intracellular calcium release, indicating the truncated NK-1R signals differently from the full-length receptor.
Gao, Xin; Frakich, Nanci; Filippini, Perla; Edwards, Laura J; Vinkemeier, Uwe; Gran, Bruno; Tanasescu, Radu; Bayraktutan, Ulvi; Colombo, Sergio; Constantinescu, Cris S ·
RPEP-06133 · 2022Out of 9 cell-penetrating peptides tested, 4 significantly improved intestinal paracellular permeability without compromising cell health. Among these, the synthetic CPPs Shuffle and Penetramax were the top performers, increasing permeability at 50 µM concentration while having only small to moderate antimicrobial effects on tested gut commensal strains. The other 4 CPPs that improved permeability had more substantial negative effects on nearly all tested gut bacteria.
Gelli, Hitesh P; Vazquez-Uribe, Ruben; Sommer, Morten Otto Alexander ·
RPEP-06136 · 2022A cyclic dipeptide made from leucine and S-benzyl cysteine (P1) self-assembled into a hydrogel at body temperature and physiological pH. The hydrogel was remarkably stable — lasting over a year without degradation, tolerating pH 6–12, and being thermoreversible.
When loaded with the cancer drug 5-fluorouracil (5FU), the hydrogel provided sustained drug release and significantly enhanced anticancer activity against colorectal cancer cells (HCT116), lowering the effective dose (IC50) of 5FU substantially. The dipeptide itself showed almost no toxicity to cancer cells even at high concentrations, making it a safe carrier material.
Ghosh, Saswati; Nag, Sayoni; Saha, Krishna Das; Banerji, Biswadip · In Vitro
RPEP-06139 · 2022The ACYP2 rs6713088 CC genotype was the standout finding: it was significantly under-represented in obese diabetics (17.8%) compared to non-obese diabetics (40.4%, p=0.01) and showed a gradient across 4 BMI grades (p=0.025). Paradoxically, the same genotype was over-represented in obese non-diabetics compared to non-obese non-diabetics (50% vs 27.6%, p=0.04), suggesting its role differs depending on diabetes status.
Ghrelin (GHRL rs27647C/T), ghrelin receptor (GHSR rs509030G/C), and TERC (rs12696304G/C) minor allele frequencies were significantly lower in normal-BMI diabetic patients (p=0.034, 0.008, and 0.011, respectively), suggesting these variants may contribute to obesity susceptibility within the diabetic population.
Giha, Hayder A; Joatar, Faris E; AlDehaini, Dhuha M B; Malalla, Zainab H A; Ali, Muhalab E; Al Qarni, Ali A ·
RPEP-06141 · 2022A peptide-mimicking ionizable lipid formulation (OH4:DOPE) successfully delivered DNA and mRNA into living tissues using ethical animal models that reduce the need for mammalian experiments. In zebrafish embryos, the lipid nanoparticles selectively transfected blood vessel endothelial cells, particularly in the endocardium (heart lining). The chicken egg membrane model also showed effective tissue transfection.
Pilot studies in mice confirmed that the transfection patterns seen in simpler models correlated with mammalian results, validating these alternative models as reliable screening tools for nucleic acid delivery systems.
Giselbrecht, Julia; Pinnapireddy, Shashank Reddy; Alioglu, Fatih; Sami, Haider; Sedding, Daniel; Erdmann, Frank; Janich, Christopher; Schulz-Siegmund, Michaela; Ogris, Manfred; Bakowsky, Udo; Langner, Andreas; Bussmann, Jeroen; Wölk, Christian · Animal Study
RPEP-06146 · 2022A 12-week skincare regimen combining a hyaluronic acid serum and a peptide-rich cream improved the appearance of sun-damaged skin on both face and neck. On the face, 79% of subjects showed improved skin texture, 50% showed reduced lines and wrinkles, and 44% showed improved skin tone. On the neck, improvements were seen in texture (68%), tone (48%), and lines/wrinkles (36%).
No adverse events were reported. All 17 subjects reported overall skin improvement and smoother-feeling skin. Eighty-eight percent said their skin looked more radiant, and 82% said it looked firmer.
Gold, Michael H; Biron, Julie A; Wilson, April; Nelson, Diane B · Open Label Clinical
RPEP-06147 · 2022Substance P dose-dependently increased metastatic activity in human SW480 colorectal cancer cells across multiple measures: MMP-2 and MMP-9 enzymatic activity increased, gene expression of both metalloproteinases was upregulated, and cell migration increased in scratch assays.
Aprepitant (a neurokinin-1 receptor antagonist) significantly reversed all substance P-mediated metastatic effects (p < 0.001). This included reduced MMP-2/MMP-9 activity at both transcriptional and translational levels and decreased cell migration. The results identify the SP/NK1R pathway as a key metastatic driver in colorectal cancer and aprepitant as a potential anti-metastatic agent.
Golestaneh, Malihe; Firoozrai, Mohsen; Javid, Hossein; Hashemy, Seyed Isaac ·
RPEP-06152 · 2022A self-microemulsifying drug delivery system (SMEDDS) using hydrophobic ion pairing achieved oral insulin absorption in diabetic rats with pharmacological availabilities of 3.23% at 50 IU/kg and 2.13% at 100 IU/kg. The optimized formulation protected insulin from gastrointestinal enzyme degradation and kept the majority of insulin within oil droplets during release. The formulation used an insulin complex with sodium n-octadecyl sulfate loaded into an optimized microemulsion with droplet sizes of 115.2 nm.
Goo, Yoon Tae; Lee, Sangkil; Choi, Ji Yeh; Kim, Min Song; Sin, Gi Hyeong; Hong, Sun Ho; Kim, Chang Hyun; Song, Seh Hyon; Choi, Young Wook ·
RPEP-06153 · 2022A multidisciplinary panel of 12 experts (endocrinologists, nephrologists, cardiologists, primary care physicians, internists, and diabetes educators) developed consensus recommendations for managing the gastrointestinal side effects of GLP-1 drugs. The guidelines cover how to properly escalate doses to reduce GI symptoms, what to do when nausea, vomiting, diarrhea, or constipation develop during treatment, and practical clinical scenarios that doctors encounter regularly. The goal is to keep patients on therapy rather than having them quit due to side effects.
Gorgojo-Martínez, Juan J; Mezquita-Raya, Pedro; Carretero-Gómez, Juana; Castro, Almudena; Cebrián-Cuenca, Ana; de Torres-Sánchez, Alejandra; García-de-Lucas, María Dolores; Núñez, Julio; Obaya, Juan Carlos; Soler, María José; Górriz, José Luis; Rubio-Herrera, Miguel Ángel ·
RPEP-06154 · 2022All five approved migraine preventive treatments demonstrated clinically relevant benefits during the first treatment week:
- Erenumab reduced weekly migraine days within 1 week (3 studies)
- Fremanezumab increased headache-free days starting Day 1 and significantly reduced migraine frequency within 1 week (6 studies)
- Galcanezumab significantly reduced the number of patients experiencing migraine beginning Day 1 and through the first week (3 studies)
- Eptinezumab reduced migraine attack likelihood on Day 1 by more than 50% versus baseline (4 studies)
- OnabotulinumtoxinA reduced headache and migraine days within 1 week (2 studies)
Four publications also reported improvements in function, disability, and quality of life as early as Week 4. No publications on traditional oral preventive agents met the criteria for early-onset prevention.
Gottschalk, Christopher; Buse, Dawn C; Marmura, Michael J; Torphy, Bradley; Pavlovic, Jelena M; Dumas, Paula K; Lalvani, Nim; Blumenfeld, Andrew ·
RPEP-06160 · 2022The researchers synthesized a flexible azaproline-tetraguanidinium transporter (FAT) that uses a non-natural peptide backbone incorporating δ-azaproline residues. This backbone provides proteolytic stability, addressing a key weakness of natural cell-penetrating peptides.
FAT adopted a random-coil structure rather than the typical polyproline helix and entered CHO cells via direct translocation. When conjugated with a proapoptotic domain peptide (14-mer) and a PDL1 morpholino antisense oligo (25-mer), FAT successfully delivered both into human carcinoma cells. Efficacy was confirmed by MTT assay (cell viability) and western blot (protein knockdown), respectively.
Gupta, Abhishek; Gupta, Shalini; Das, Ujjal; Sinha, Surajit ·
RPEP-06161 · 2022The review found that acylated ghrelin levels positively correlate with alcohol-induced brain responses in the ventral striatum — a key reward processing area — in both the right and left hemispheres. This suggests ghrelin signaling directly amplifies the brain's reward response to alcohol.
GHSR-1A antagonism has been shown in preclinical and early clinical studies to suppress artificial reward circuitries and promote self-control for alcohol consumption. Notably, GHSR-1A also exhibits ligand-independent constitutive activity, meaning it can activate reward pathways even without ghrelin binding — which may explain why some people experience persistent cravings.
Gupta, Shreyasi; Mukhopadhyay, Sanchari; Mitra, Arkadeep ·
RPEP-06165 · 2022Detecting peptide doping is one of the hardest challenges in anti-doping science because many performance-enhancing peptides have extremely short half-lives and are identical or nearly identical to natural hormones. This review covers the analytical strategies used to detect banned peptides from WADA sections S2 (peptide hormones and growth factors), S4 (hormone and metabolic modulators), and S5 (diuretics and masking agents).
The key detection tools include solid-phase peptide synthesis (SPPS) to create reference standards and isotopically labeled analogs for quantification, combined with liquid chromatography-high resolution mass spectrometry (LC-HRMS) for analysis in biological samples like blood and urine.
Gómez-Guerrero, Néstor Alejandro; González-López, Nicolás Mateo; Zapata-Velásquez, Juan Diego; Martínez-Ramírez, Jorge Ariel; Rivera-Monroy, Zuly Jenny; García-Castañeda, Javier Eduardo · Review
RPEP-06175 · 2022After single intravenous and intramuscular administration, BPC-157 showed a very short elimination half-life of less than 30 minutes in both rats and beagle dogs. Pharmacokinetics were linear across all tested doses. Mean absolute bioavailability after intramuscular injection was approximately 14-19% in rats and 45-51% in beagle dogs.
Using tritium-labeled ([³H]) BPC-157, the researchers tracked the peptide's fate in the body. It was rapidly metabolized into small peptide fragments that were further broken down into individual amino acids entering normal metabolic pathways. The primary excretion routes were urine and bile. These findings represent the first comprehensive pharmacokinetic characterization of BPC-157.
He, Lei; Feng, Donglin; Guo, Hui; Zhou, Yueyuan; Li, Zhaozhao; Zhang, Kuo; Zhang, Wangqian; Wang, Shuning; Wang, Zhaowei; Hao, Qiang; Zhang, Cun; Gao, Yuan; Gu, Jintao; Zhang, Yingqi; Li, Weina; Li, Meng ·
RPEP-06178 · 2022The chiral peptide supramolecule DPAICP@ME (D-peptide Au(I) infinite covalent polymer camouflaged with milk extracellular vesicle membranes) demonstrated:
- Stability through gastrointestinal absorption and blood circulation after oral administration
- Satisfactory tumor accumulation via oral medication
- Restoration of p53 signaling pathway for cancer therapy
- Efficacy across three cancer models: B16F10 melanoma homograft, LLC Lewis orthotopic lung cancer, and patient-derived orthotopic xenograft (PDOX) colon cancer
- Enhancement of anti-PD1 immunotherapy through further T-cell activation when used in combination
He, Wangxiao; Zhang, Zhang; Yang, Wenguang; Zheng, Xiaoqiang; You, Weiming; Yao, Yu; Yan, Jin; Liu, Wenjia ·