RPEP-04887 · 2020Salmon skin collagen was broken down by four different enzymes. The trypsin-digested version showed the strongest DPP-IV inhibition at 66% at 10 mg/mL.
After separating the fragments by size, the smallest fraction (under a certain molecular weight) had an IC50 of 0.79 mg/mL. Further purification identified a novel peptide, LDKVFR, with an IC50 of 0.1 mg/mL (128.71 micromolar).
Molecular docking showed LDKVFR binds to DPP-IV through six hydrogen bonds and eight hydrophobic interactions, explaining its inhibitory activity.
Jin, Ritian; Teng, Xiangyu; Shang, Jiaqi; Wang, Dangfeng; Liu, Ning · In Vitro
RPEP-04888 · 2020Tumor-infiltrating lymphocytes from 9 of 12 patients (75%) contained CD8+ T cells that recognized Merkel cell polyomavirus T-antigen. Each patient's immune cells recognized between 1 and 8 different viral epitopes.
Analysis of 16 identified epitopes showed that 97% of patients with virus-positive Merkel cell carcinoma had the HLA alleles needed to mount CD8+ T cell responses against the viral proteins.
The amino acid region 70-110 of the large T antigen was especially rich in immune targets, while the oncogenic domains were not commonly recognized. This is important because a vaccine could focus on the immunogenic region while avoiding the cancer-causing parts.
Jing, Lichen; Ott, Mariliis; Church, Candice D; Kulikauskas, Rima M; Ibrani, Dafina; Iyer, Jayasri G; Afanasiev, Olga K; Colunga, Aric; Cook, Maclean M; Xie, Hong; Greninger, Alexander L; Paulson, Kelly G; Chapuis, Aude G; Bhatia, Shailender; Nghiem, Paul; Koelle, David M · Human Tissue Study
RPEP-04889 · 2020Cyclic peptides offer a middle ground between small molecule drugs and large biologics. Their ring structure gives them better cell permeability and metabolic stability compared to linear peptides, while still allowing them to bind large protein surfaces that small molecules cannot reach.
More than 40 cyclic peptide drugs have reached clinical approval, most derived from natural products. Newer approaches including rational design, mRNA display, phage display, and DNA-encoded libraries are creating cyclic peptides against targets that nature never addressed.
The review covers multiple macrocyclization strategies including disulfide bonds, lactam bridges, hydrocarbon stapling, and click chemistry, each with different trade-offs in terms of stability, permeability, and ease of synthesis.
Jing, Xiaoshu; Jin, Kang · Review
RPEP-04890 · 2020Annual per-patient costs were similar across all four GLP-1 receptor agonists in the UK market. However, once-weekly semaglutide consistently outperformed the others in getting patients to treatment goals.
For the composite endpoint of HbA1c below 7.0% without weight gain or low blood sugar episodes, the competing drugs fell short: exenatide ER was 50.0% less effective, liraglutide was 51.3% less effective, and dulaglutide was 21.6% less effective than semaglutide.
Semaglutide also led in single endpoints including HbA1c targets (below 7.0% and below 7.5%) and meaningful weight loss (5% or more body weight reduction).
Johansen, Pierre; Sandberg, Anna; Capehorn, Matthew · Cost Effectiveness Analysis
RPEP-04891 · 2020Compared to placebo, liraglutide 3 mg daily significantly reduced how much food participants wanted to eat, their desire for sweet, salty, savory, and fatty foods, and the maximum volume of a nutrient drink they could tolerate. Participants also reported feeling fuller after meals.
Liraglutide increased postprandial PYY levels (a satiety hormone) while decreasing active GLP-1 levels relative to baseline. This suggests the drug changes the gut hormone environment beyond just mimicking GLP-1.
Body composition scans showed significant reductions in total body fat, trunk fat, and both upper and lower body fat. Lean body mass was preserved, meaning the weight lost was predominantly fat.
Kadouh, Hoda; Chedid, Victor; Halawi, Houssam; Burton, Duane D; Clark, Matthew M; Khemani, Disha; Vella, Adrian; Acosta, Andres; Camilleri, Michael · Randomized Controlled Trial
RPEP-04892 · 2020The team used a "tail-to-side chain" stapling method to create a library of modified peptides. These stapled peptides modulated the self-association and fibril formation of amyloid-beta 1-40, the protein fragment central to Alzheimer's pathology.
The stapled peptides also disrupted preformed fibrillar aggregates, converting them into non-toxic species. This dual action, preventing new aggregation and breaking up existing fibrils, is particularly valuable.
The ring shape made the peptides significantly more resistant to proteolytic enzymes, which would normally break down linear peptides quickly. This improved stability is essential for any potential therapeutic use.
Kalita, Sujan; Kalita, Sourav; Paul, Ashim; Sarkar, Amar; Mandal, Bhubaneswar · In Vitro
RPEP-04894 · 2020The SIWV peptide was identified from an isoform of annexin-A3, a human membrane-interacting protein. It showed remarkable specificity for glioblastoma tissue both in cell cultures and in living mice.
The peptide enters cells through a caveolin-mediated endocytosis pathway, confirmed through receptor inhibition and genetic knockdown experiments.
When grafted onto porous silicon nanoparticles loaded with the cancer drug SN-38, SIWV-targeted nanoparticles showed significantly better tumor targeting than scrambled-peptide controls in a mouse brain tumor model. The treatment also showed statistically significant anti-tumor efficacy (P < 0.05) compared to free SN-38.
Kang, Rae Hyung; Jang, Jeong-Eun; Huh, Eugene; Kang, Seong Jae; Ahn, Dae-Ro; Kang, Jae Seung; Sailor, Michael J; Yeo, Seung Geun; Oh, Myung Sook; Kim, Dokyoung; Kim, Hyo Young · Animal Study
RPEP-04895 · 2020The team started with a known all-D linear peptide that potently inhibits the p53-Mdm2 interaction in a test tube but cannot enter cells. Using computational modeling, they designed optimal staple placement to create macrocyclic versions.
The resulting stapled and stitched all-D peptides showed increased alpha-helical structure, improved binding to the Mdm2 target, complete resistance to proteolytic enzymes, and, most importantly, cellular activity.
This represents the first demonstration that combining D-amino acids with hydrocarbon stapling can produce peptides that are both enzyme-proof and cell-permeable, overcoming two of the biggest barriers to peptide drug development.
Kannan, Srinivasaraghavan; Aronica, Pietro G A; Ng, Simon; Gek Lian, Dawn Thean; Frosi, Yuri; Chee, Sharon; Shimin, Jiang; Yuen, Tsz Ying; Sadruddin, Ahmad; Kaan, Hung Yi Kristal; Chandramohan, Arun; Wong, Jin Huei; Tan, Yaw Sing; Chang, Zi Wei; Ferrer-Gago, Fernando J; Arumugam, Prakash; Han, Yi; Chen, Shiying; Rénia, Laurent; Brown, Christopher J; Johannes, Charles W; Henry, Brian; Lane, David P; Sawyer, Tomi K; Verma, Chandra S; Partridge, Anthony W · In Vitro
RPEP-04896 · 2020Mice were fed a high-fat, high-fructose, high-cholesterol diet for 36 weeks to develop NASH with fibrosis, then treated for 8 weeks. Low-dose glucagon or GIP alone did not affect body weight, liver fat, or liver damage scores. But when combined with GLP-1 receptor activation, both glucagon and GIP provided additional benefits.
The triple combination (GLP-1 + glucagon + GIP) and a dual GLP-1/glucagon peptide both significantly reduced the NAFLD activity score more than high-dose liraglutide. This happened at comparable levels of weight loss, meaning the extra liver improvement came from the hormones themselves, not just from losing weight.
This supports the idea that multi-receptor agonists targeting two or three gut hormone receptors could be more effective for NASH than GLP-1 drugs alone.
Kannt, Aimo; Madsen, Andreas Nygaard; Kammermeier, Claire; Elvert, Ralf; Klöckener, Tim; Bossart, Martin; Haack, Torsten; Evers, Andreas; Lorenz, Katrin; Hennerici, Wolfgang; Rocher, Corinne; Böcskei, Zsolt; Guillemot, Jean-Claude; Mikol, Vincent; Pattou, Francois; Staels, Bart; Wagner, Michael · Animal Study
RPEP-04898 · 2020Plasma BNP levels increased more than fivefold during therapeutic hypothermia (logarithmically from 1.98 to 2.63, P < 0.01). This was a highly significant change observed across the 21 patients.
During cooling, diastolic pulmonary artery pressure actually decreased, and stroke volume index did not change significantly. This means the BNP increase was not driven by the usual triggers of cardiac stress or fluid overload.
In contrast to BNP, ANP (atrial natriuretic peptide) showed minimal change during cooling. This selective BNP response suggests a specific mechanism linking cold exposure to BNP release from the heart.
Kashiwagi, Yusuke; Komukai, Kimiaki; Kimura, Haruka; Okuyama, Toraaki; Maehara, Tomoki; Fukushima, Keisuke; Kamba, Takahito; Oki, Yoshitsugu; Shirasaki, Keisuke; Kubota, Takeyuki; Miyanaga, Satoru; Nagoshi, Tomohisa; Yoshimura, Michihiro · Observational
RPEP-04899 · 2020ANP and BNP are released by the heart in response to increased pressure or volume. They lower blood pressure and reduce fluid retention through specific receptors. CNP is produced by blood vessel walls and acts locally to protect blood vessels.
Beyond lowering blood pressure, natriuretic peptides also reduce the organ damage caused by hypertension, including heart enlargement, kidney damage, and blood vessel stiffening.
Neprilysin is the enzyme that degrades natriuretic peptides. Blocking neprilysin with drugs increases the activity of the body's own peptides. A dual inhibitor combining neprilysin inhibition with an angiotensin receptor blocker (sacubitril/valsartan) has been approved for heart failure, and clinical data shows neprilysin inhibition also benefits hypertension patients.
Kato, Johji · Review
RPEP-04900 · 2020Teriparatide prevents ovariectomy-induced bone loss, reduces mechanical hyperalgesia, and suppresses CGRP and TRPV1 upregulation in dorsal root ganglion neurons innervating affected limbs.
Kato, Sho; Wakabayashi, Hiroki; Nakagawa, Taro; Miyamura, Gaku; Naito, Yohei; Iino, Takahiro; Sudo, Akihiro · Animal Study
RPEP-04901 · 2020The antibody-drug conjugate P38B-DM1 was constructed using a mouse-canine chimeric antibody (P38B) that targets dog podoplanin, a peptide linker, and the cytotoxic payload emtansine (DM1). Construction used the chemical conjugation by affinity peptide (CCAP) method.
In cell culture, P38B-DM1 killed podoplanin-overexpressing cells in a dose-dependent manner. In a mouse xenograft model, P38B-DM1 showed significantly higher anti-tumor activity than the antibody alone (P38B).
The peptide linker and CCAP conjugation method allowed controlled attachment of the drug to the antibody, which is critical for consistent drug-to-antibody ratios.
Kato, Yukinari; Ito, Yuji; Ohishi, Tomokazu; Kawada, Manabu; Nakamura, Takuro; Sayama, Yusuke; Sano, Masato; Asano, Teizo; Yanaka, Miyuki; Okamoto, Saki; Handa, Saori; Komatsu, Yu; Takei, Junko; Kaneko, Mika K · Animal Study
RPEP-04903 · 2020Penetratin enhanced the delivery of salmon calcitonin (sCT) through both TR146 buccal cell layers and porcine buccal tissues in a concentration-dependent manner.
FITC-labeled Penetratin showed rapid intracellular uptake at low concentrations (0-15 micromolar) with a more gradual increase above 15 micromolar. The uptake of sCT increased alongside Penetratin concentration.
At 12.2 micromolar, Penetratin enhanced sCT flux 5.5-fold through TR146 cell layers and 93.7-fold through porcine buccal tissue. The dramatically higher enhancement in actual tissue suggests Penetratin works particularly well in the multi-layered environment of real buccal mucosa.
Keum, Taekwang; Noh, Gyubin; Seo, Jo-Eun; Bashyal, Santosh; Lee, Sangkil · In Vitro
RPEP-04904 · 2020In normal rats, substance P increased GABA release in the central amygdala, and blocking the NK-1 receptor decreased it. This shows substance P regulates baseline brain activity in this region.
In alcohol-dependent rats, substance P triggered a larger increase in GABA release despite reduced NK-1 receptor expression. This paradox (fewer receptors but bigger response) indicates receptor hypersensitivity, meaning each remaining receptor was overreacting to substance P.
Critically, the NK-1 receptor antagonist blocked alcohol-induced GABA release in dependent and withdrawn rats but not in normal rats. This means chronic alcohol exposure recruits the substance P system to mediate alcohol's effects on the brain, a mechanism that persists into protracted withdrawal.
Khom, S; Steinkellner, T; Hnasko, T S; Roberto, M · Animal Study
RPEP-04905 · 2020Thymosin beta-4 treatment activated human adipose-derived stem cells by upregulating PI3K/AKT/mTOR and MAPK/ERK signaling pathways. It also increased cell migration, sprouting from microbeads, and endothelial differentiation potential.
In a dorsal window chamber model, the combination of thymosin beta-4 and stem cells produced significantly more microvessel branches than stem cells alone.
In the ischemic hindlimb model, mice receiving both thymosin beta-4 and stem cells had improved blood flow recovery and less limb or foot loss compared to stem cells alone. This suggests the peptide primes the stem cells to be more effective at building new blood vessels.
Kim, Jong-Ho; Lim, I-Rang; Park, Chi-Yeon; Joo, Hyung Joon; Noh, Ji-Min; Choi, Seung-Cheol; Hong, Soon Jun; Lim, Do-Sun · Animal Study
RPEP-04906 · 2020LBLP triggered endogenous nitric oxide (NO) production in Candida albicans through the NO synthase pathway. This nitric oxide overwhelmed the cell's glutathione defense system, leading to nitrosative stress.
The excess NO inhibited mitochondrial respiration and altered NAD+/NADH ratios. This disrupted the mitochondrial membrane potential, caused calcium homeostasis failure, and led to mitochondrial superoxide accumulation.
The cascade ultimately triggered apoptosis (programmed cell death) in the fungal cells. When researchers blocked NO production, all of these effects were reduced, confirming that NO is the central mechanism of LBLP's antifungal action.
Kim, Suhyun; Hwang, Jae Sam; Lee, Dong Gun · In Vitro
RPEP-04907 · 2020Dendritic cells pulsed with CTP-fused tumor antigens (WT1 and BIRC5) showed enhanced expression of MHC molecules and co-stimulatory markers, indicating better antigen presentation. The vaccine also shifted immune signaling toward Th1 cytokine polarization, which favors anti-tumor immunity.
The CTP-fused antigen approach increased the number of IFN-gamma-producing effector T cells. These T cells showed enhanced killing of glioblastoma target cells expressing the matching antigens.
Combining the vaccine with PD-1 blockade further improved the cytotoxic T lymphocyte response, suggesting the two approaches work better together than either alone.
Kim, Young-Hee; Tran, Thi-Anh-Thuy; Duong, Thi-Hoang-Oanh; Jung, Shin; Kim, In-Young; Moon, Kyung-Sub; Jang, Woo-Youl; Lee, Hyun-Ju; Lee, Je-Jung; Jung, Tae-Young · In Vitro
RPEP-04908 · 2020Systemically administered recombinant hBD2 showed therapeutic efficacy in three distinct colitis models: DSS-induced mucosal injury, TNBS-induced loss of mucosal tolerance, and T-cell transfer colitis. In all three models, hBD2 reduced inflammation, improved disease activity index, and prevented colitis-induced weight loss.
The effectiveness matched anti-TNF-alpha treatment and steroids, which are current standard-of-care therapies for inflammatory bowel disease.
Mechanistically, hBD2 targeted dendritic cells through the CCR2 receptor. It decreased NF-kB phosphorylation (the main inflammatory switch) and increased CREB phosphorylation in these cells, effectively reprogramming them from pro-inflammatory to anti-inflammatory. This is the first study showing in vivo efficacy of a systemically administered defensin.
Koeninger, Louis; Armbruster, Nicole S; Brinch, Karoline Sidelmann; Kjaerulf, Søren; Andersen, Birgitte; Langnau, Carolin; Autenrieth, Stella E; Schneidawind, Dominik; Stange, Eduard F; Malek, Nisar P; Nordkild, Peter; Jensen, Benjamin A H; Wehkamp, Jan · Animal Study
RPEP-04909 · 2020Across 49 acute studies, protein significantly reduced hunger (-7 mm on visual scale, P<0.001), desire to eat (-5 mm, P=0.045), and prospective food consumption (-5 mm, P=0.001). It increased fullness (+10 mm, P<0.001) and satiety (+4 mm, P<0.001).
For gut hormones, protein decreased ghrelin (-20 pg/mL, P<0.001) and increased both cholecystokinin (+30 pg/mL, P<0.001) and GLP-1 (+21 ng/mL, P<0.001). Peptide YY and GIP were not significantly affected.
There was a dose threshold: appetite feelings changed at doses under 35 grams, but the hormonal changes (ghrelin, CCK, GLP-1) only became significant at 35 grams or more. Long-term protein intake showed no consistent effects except a decrease in GLP-1.
Kohanmoo, Ali; Faghih, Shiva; Akhlaghi, Masoumeh · Meta Analysis
RPEP-04910 · 2020Combining multiple gut peptide receptor agonists (dual or triple) produces additive weight loss and glycemic improvement, replicating the hormonal changes seen after bariatric surgery.
Koliaki, Chrysi; Liatis, Stavros; Dalamaga, Maria; Kokkinos, Alexander · Review
RPEP-04912 · 2020Cell-penetrating peptides must escape endosomes to deliver cargo to the cytoplasm. The researchers found that some CPP delivery protocols activate three cellular stress responses: Chmp1b (endosomal repair), Galectin-3 (organelle clearance), and TFEB (biogenesis).
These same protocols also modulated endocytosis rates and endocytic proteolysis, suggesting that some CPPs disrupt normal cell trafficking.
Remarkably, a multimeric analogue of TAT (the most commonly used CPP) achieved efficient endosomal escape without triggering any of these membrane damage responses. This challenges the assumption that endosomal leakiness equals toxicity and shows that clean cytoplasmic delivery is achievable.
Kondow-McConaghy, Helena M; Muthukrishnan, Nandhini; Erazo-Oliveras, Alfredo; Najjar, Kristina; Juliano, Rudolph L; Pellois, Jean-Philippe · In Vitro
RPEP-04913 · 2020This is a protocol for a two-stage pilot randomized controlled trial. In stage one (weeks 0-12), 60 ASD patients receive either oral L. reuteri probiotics or placebo. In stage two (weeks 13-24), all participants also receive intranasal oxytocin spray.
Primary outcomes include serum oxytocin levels, social behavior scores (Autism Behavior Checklist, Social Responsiveness Scale), an emotional facial matching test, and eye-tracking. Secondary outcomes include GI function, gut microbiome composition, and short-chain fatty acid levels.
The rationale is based on animal studies showing L. reuteri increases oxytocin levels and improves social behavior in ASD mouse models. Intranasal oxytocin has shown some promise in improving social functioning in ASD patients.
Kong, Xue-Jun; Liu, Jun; Li, Jing; Kwong, Kenneth; Koh, Madelyn; Sukijthamapan, Piyawat; Guo, Jason J; Sun, Zhenyu Jim; Song, Yiqing · Trial Protocol
RPEP-04915 · 2020RNase 7 combined with human self-DNA strongly induced IP-10 production in keratinocytes. Notably, two other antimicrobial peptides (human beta-defensin 2 and LL-37) combined with DNA did not produce this effect, showing RNase 7 has a unique ability.
The IP-10 production was mediated through type I interferon (IFN-beta) induction and the STING pathway (stimulator of interferon genes). Blocking the interferon receptor or STING significantly reduced the response.
Pretreating keratinocytes with RNase 7 and DNA significantly reduced herpes simplex virus-1 infection, demonstrating a direct antiviral protective function. RNase 7 functions as an alarmin that converts self-DNA into a danger signal activating innate antiviral immunity directly in skin cells.
Kopfnagel, Verena; Dreyer, Sylvia; Baumert, Kathrin; Stark, Maximilian; Harder, Jürgen; Hofmann, Karsten; Kleine, Michael; Buch, Anna; Sodeik, Beate; Werfel, Thomas · In Vitro
RPEP-04916 · 2020Multiple plant defensin (PDF) genes were strongly induced in Arabidopsis when the fungal pathogen Colletotrichum tropicale invaded plant cells. A necrotrophic pathogen, Alternaria brassicicola, also triggered PDF expression upon invasion.
In edr1 mutant plants, defensin expression after pathogen invasion was significantly reduced, showing that EDR1 protein kinase is required for this defense response. Similarly, ora59 mutant plants failed to properly induce defensin expression after invasion.
Inoculation assays with A. brassicicola showed that ORA59 is directly involved in post-invasion resistance. Plants lacking ORA59 were more susceptible to the fungal pathogen, linking defensin expression to actual disease resistance.
Kosaka, Ayumi; Suemoto, Haruka; Singkaravanit-Ogawa, Suthitar; Takano, Yoshitaka · In Vitro
RPEP-04917 · 2020The team developed heterodimeric peptide arrays where a cell-penetrating peptide (CPP) and a functional peptide are linked by a disulfide bond. Inside cells, the reducing environment breaks this bond, releasing the functional peptide to act independently.
The synthesis method used Fmoc-Lys(ivDde)-OH to build both peptides on a single molecule and selectively form the disulfide bond. This enabled efficient production of CPP-functional peptide heterodimers.
Using this system to screen single amino acid substitutions of a cell-death-inducing peptide (WELVVLGKL), they identified 6 variants with higher activity than the original. This demonstrates the system's utility for optimizing intracellular peptide functions.
Kozaki, Ikko; Shimizu, Kazunori; Honda, Hiroyuki · In Vitro
RPEP-04918 · 2020Dermal endothelial cells in rosacea showed increased VCAM1 expression. The researchers found that UVB-exposed keratinocytes produced double-stranded RNA that, in the presence of LL-37, induced adhesion molecules on endothelial cells.
Sequencing revealed activation of pathways directly relevant to rosacea: type I and II interferon signaling, cell-cell adhesion, leukocyte chemotaxis, and angiogenesis.
The double-stranded RNA + LL-37 combination promoted monocyte adhesion and transmigration across endothelial cell layers. Knocking down TLR3, RIGI, or IRF1 reduced monocyte adhesion, confirming the RNA recognition pathway is the key mechanism.
Kulkarni, Nikhil N; Takahashi, Toshiya; Sanford, James A; Tong, Yun; Gombart, Adrian F; Hinds, Brian; Cheng, Joyce Y; Gallo, Richard L · In Vitro
RPEP-04919 · 2020Many drugs fail because they are broken down too quickly by enzymes or cannot get inside cells where they need to work. PEGylation addresses the first problem by shielding molecules from degradation and kidney clearance. CPPs address the second by ferrying cargo across cell membranes.
However, CPPs themselves are peptides and suffer from rapid degradation. PEGylating CPPs can protect them while preserving their cell-penetrating ability.
The review covers PEGylated CPP formulations used in drug delivery for cancer, gene therapy, protein delivery, and other biomedical applications. It discusses the trade-offs between PEG chain length, CPP type, and overall delivery efficiency.
Kumar, Sumit; Singh, Devender; Kumari, Pooja; Malik, Rajender Singh; Poonam; Parang, Keykavous; Tiwari, Rakesh Kumar · Review
RPEP-04920 · 202045% of SLE patients had circulating T cells that responded strongly to LL37. These T cell levels correlated with anti-LL37 antibody levels and disease activity.
Unlike psoriasis, where LL37-specific T cells are Th17 cells, the SLE LL37-specific T cells displayed a T-follicular helper (TFH)-like phenotype with CXCR5, Bcl-6, and IL-21 expression. This profile is designed to help B cells produce antibodies.
Citrullinated LL37 (cit-LL37) was found abundantly in SLE tissues (skin and kidney). SLE T cells showed much stronger reactivity to cit-LL37 compared to native LL37. In functional assays, these T cells promoted B cell secretion of pathogenic anti-LL37 antibodies.
Lande, R; Palazzo, R; Gestermann, N; Jandus, C; Falchi, M; Spadaro, F; Riccieri, V; James, E A; Butera, A; Boirivant, M; Feldmeyer, L; Surbeck, I; Di Lucca, J; Stuber, F; Spinelli, F R; Botti, E; Marinari, B; Bianchi, L; Pica, R; Cerbelli, B; Giannakakis, K; Auteri, S E; Daniels, I; Durrant, L G; Horstman, S; Costanzo, A; Romero, P; Alessandri, C; Conti, F; Valesini, G; Gilliet, M; Chizzolini, C; Frasca, L · Human Observational
RPEP-04921 · 2020Six recombinant antibodies (MRB137-MRB142) were produced as monovalent mouse antibodies with scFv portions fused to mouse IgG2a Fc. These antibodies can specifically recognize either native LL37 or citrullinated LL37 and do not cross-react with carbamylated LL37.
Using ELISA, the antibodies detected native LL37 or citrullinated LL37 in serum samples from SLE and rheumatoid arthritis patients. Immunohistochemistry detected these forms in skin tissue from cutaneous lupus patients.
These antibodies are previously unavailable tools that can now be used to study the relationship between post-translationally modified LL37 and immune system activation in chronic autoimmune diseases.
Lande, Roberto; Palazzo, Raffaella; Hammel, Philippe; Pietraforte, Immacolata; Surbeck, Isabelle; Gilliet, Michel; Chizzolini, Carlo; Frasca, Loredana · Tool Development
RPEP-04922 · 2020The method combined robotic-assisted near-infrared hematocrit measurement with fully automated strong cation exchange solid-phase extraction. This enabled detection of 46 lower molecular mass (<2 kDa) peptide and non-peptide doping agents by LC-HRMS.
Target analytes included agonists of the gonadotropin-releasing hormone receptor, ghrelin receptor, growth hormone receptor, and antidiuretic hormone receptor. Several glycine derivatives of GHRPs, designed to evade current testing, were also covered.
Validation met WADA guidelines with LODs between 0.5 and 20 ng/mL. Proof of concept was demonstrated with authentic post-administration samples containing GHRP-2 and GHRP-6. The method also worked with blood collected by microneedle devices from the upper arm.
Lange, Tobias; Thomas, Andreas; Walpurgis, Katja; Thevis, Mario · Method Development
RPEP-04923 · 2020Calves orally inoculated with EHEC O157:H7 showed neutrophil infiltration in the ileum and recto-anal junction at 7 and 14 days post-infection. Mucin layers and mast cell populations were altered across the small and large intestines.
There were differential expression changes in key bovine beta-defensins: tracheal antimicrobial peptide (TAP) was altered in the ileum, and lingual antimicrobial peptide (LAP) was changed in the recto-anal junction. TLR4, the main receptor for detecting E. coli's lipopolysaccharide, was downregulated in the recto-anal junction.
Gut bacterial communities were also affected, with changes in Negativibacillus and Erysipelotrichaceae abundance in rectal mucosa-associated bacteria. All of this occurred without major clinical signs.
Larzábal, Mariano; Da Silva, Wanderson Marques; Multani, Anmol; Vagnoni, Lucas E; Moore, Dadin P; Marin, Maia S; Riviere, Nahuel A; Delgado, Fernando O; Vilte, Daniel A; Victorica, Matias Romero; Ma, Tao; Le Guan, Luo; Talia, Paola; Cataldi, Angel; Cobo, Eduardo R · Animal Study
RPEP-04924 · 2020The pain caused by Phoneutria nigriventer venom is mediated through both peripheral and central mechanisms, involving B2 receptors, serotonin (5-HT4), glutamate (NMDA/AMPA), tachykinin (NK1/NK2), sodium channels (TTX-sensitive), acid-sensing channels (ASIC), and TRPV1 channels.
Despite the venom's pain-causing nature, seven individual toxins (omega-CNTX-Pn4a, omega-CNTX-Pn2a, omega-CNTX-Pn3a, kappa-CNTX-Pn1a, U7-CNTX-Pn1a, delta-CNTX-Pn1a, Gamma-CNTX-Pn1a) and a semi-synthetic peptide (PnPP-19) have shown consistent antinociceptive (pain-relieving) properties in experimental pain models.
The pain-relieving toxins work through mechanisms including calcium channel blockade, potassium channel activation, and modulation of opioid receptors.
Lauria, Pedro Santana Sales; Villarreal, Cristiane Flora; Casais-E-Silva, Luciana Lyra · Review
RPEP-04925 · 2020Endomorphin-1 and endomorphin-2 showed a bias toward cAMP signaling at the mu opioid receptor (MOR), while dynorphin-B showed a bias toward G-protein (35S-GTPgammaS) signaling. This pattern was consistent across multiple cell lines expressing human MOR.
The researchers investigated whether RGS-4 (a G-protein regulator) or adenylyl cyclase 6 (AC6) might explain the endomorphin bias. However, neither an RGS-4 inhibitor nor AC6 knockdown significantly changed the bias profile, ruling out these specific mechanisms.
Biased agonism at opioid receptors is important because different signaling pathways may lead to different physiological effects. Pain relief, euphoria, respiratory depression, and constipation are thought to be mediated by different downstream pathways.
LaVigne, Justin; Keresztes, Attila; Chiem, Daniel; Streicher, John M · In Vitro
RPEP-04926 · 2020Venom-derived peptide toxins possess optimized pharmaceutical properties — high selectivity, potency, protease resistance, and low immunogenicity — making them ideal drug leads with several already approved.
Lazarovici, Philip · Review
RPEP-04927 · 2020Intranasal oxytocin (24 IU) enhanced emotional empathy responses to both positive and negative emotional stimuli in the Multifaceted Empathy Task, replicating previous findings across multiple cultures.
Eye-tracking revealed the mechanism: oxytocin increased the proportion of time participants spent viewing the faces of people in the pictures and decreased time spent viewing body posture and background context.
This suggests oxytocin does not directly amplify emotional processing. Instead, it redirects visual attention toward the most informative social cue (the face), which naturally leads to stronger empathic responses.
Le, Jiao; Kou, Juan; Zhao, Weihua; Fu, Meina; Zhang, Yingying; Becker, Benjamin; Kendrick, Keith M · Randomized Controlled Trial
RPEP-04928 · 2020The native PYY peptide has a very short half-life, making it impractical as a medication. Using combined peptide stapling and PEG-fatty acid conjugation, the researchers created potent PYY analogs that activate the NPY2 receptor and have rat half-lives exceeding 14 hours.
The 14-hour rat half-life is expected to translate to a human half-life suitable for once-weekly dosing, which would be practical for patients.
The lead candidate (compound 22) combined with a long-acting GLP-1 analog showed excellent efficacy in a diet-induced obesity mouse model for three key outcomes: glucose control, food intake reduction, and body weight loss. This combination approach mimics the hormonal changes seen after bariatric surgery.
Lear, Sam; Pflimlin, Elsa; Zhou, Zhihong; Huang, David; Weng, Sharon; Nguyen-Tran, Van; Joseph, Sean B; Roller, Shane; Peterson, Scott; Li, Jing; Tremblay, Matthew; Schultz, Peter G; Shen, Weijun · Animal Study
RPEP-04929 · 2020A symmetrically stapled exendin-4 analog with an integrated albumin-binding motif showed excellent blood sugar and body weight reduction in diabetic/obese mice.
Lear, Sam; Seo, Hyosuk; Lee, Candy; Lei, Lei; Amso, Zaid; Huang, David; Zou, Huafei; Zhou, Zhihong; Nguyen-Tran, Vân T B; Shen, Weijun · Animal Study
RPEP-04930 · 2020LBLP kills E. coli through ROS-induced apoptosis-like death rather than membrane disruption, and shows no hemolytic toxicity to human erythrocytes.
Lee, B; Hwang, J S; Lee, D G · In Vitro
RPEP-04931 · 2020S. pseudintermedius from otitis externa cases were more resistant to the canine cathelicidin K9CATH than strains from healthy dogs, despite similar biofilm-forming ability.
Lee, Gi Yong; Yang, Soo-Jin · In Vitro
RPEP-04932 · 2020A GM-CSF→CCL17 pathway in macrophages drives inflammatory pain through nerve growth factor, CGRP, and substance P signaling in non-bone-marrow-derived cells.
Lee, Kevin M-C; Jarnicki, Andrew; Achuthan, Adrian; Fleetwood, Andrew J; Anderson, Gary P; Ellson, Christian; Feeney, Maria; Modis, Louise K; Smith, Julia E; Hamilton, John A; Cook, Andrew · Animal Study
RPEP-04933 · 2020L. casei-immunized black soldier fly larval extract produced cecropin and defensin peptides that inhibited Salmonella at 100-200 µg/100 µL with no cytotoxicity up to 40,000 µg/100 µL.
Lee, Kyu-Shik; Yun, Eun-Young; Goo, Tae-Won · In Vitro
RPEP-04934 · 2020PF-5190457 did not significantly alter blood levels of 13 hormones (including insulin, GLP-1, cortisol, thyroid hormones, and leptin) during dosing or alcohol co-administration.
Lee, Mary R; Farokhnia, Mehdi; Cobbina, Enoch; Saravanakumar, Anitha; Li, Xiaobai; Battista, Jillian T; Farinelli, Lisa A; Akhlaghi, Fatemeh; Leggio, Lorenzo · Phase 1 Clinical Trial
RPEP-04935 · 2020Nearly one-third of experimentally validated T cell tumor antigens have MHC binding affinities (IC50 > 500 nM) below standard prediction cutoffs, highlighting the limitations of in silico approaches.
Lee, Maxwell Y; Jeon, Jun W; Sievers, Cem; Allen, Clint T · Review
RPEP-04936 · 2020Resolvin D3 reversed psoriasiform itch and prevented skin inflammation by inhibiting TRPV1 and reducing CGRP in sensory neurons, with confirmed activity in human DRG neurons.
Lee, Sang Hoon; Tonello, Raquel; Im, Sang-Taek; Jeon, Hawon; Park, Jeongsu; Ford, Zachary; Davidson, Steve; Kim, Yong Ho; Park, Chul-Kyu; Berta, Temugin · Animal Study
RPEP-04937 · 2020A photoreactive Fc-binding peptide achieved site-specific conjugation to trastuzumab at Glu-382, enabling precise DAR 2 antibody-drug conjugate formation via click chemistry.
Lee, TaeJin; Kim, Ju Hwan; Kwon, Se Jeong; Park, Sun Hee; Kim, Jinyoung; Kang, Hyo Jin; Chung, Sang J · In Vitro
RPEP-04938 · 2020PAMAM dendrimer nanoparticles decorated with both TAIP (anti-inflammatory peptide) and CPP (cell-penetrating peptide) improved mortality and organ damage in septic mice.
Lee, Wonhwa; Park, Eun Ji; Kwon, Oh Kwang; Kim, Hyelim; Yoo, Youngbum; Kim, Shin-Woo; Seo, Young-Kyo; Kim, In-San; Na, Dong Hee; Bae, Jong-Sup · Animal Study
RPEP-04939 · 2020Short-term inflammation reduces neuronal substance P responsiveness while long-term low-dose inflammation enhances glutamate sensitivity, with microglia driving the inflammatory cascade.
Leisengang, Stephan; Nürnberger, Franz; Ott, Daniela; Murgott, Jolanta; Gerstberger, Rüdiger; Rummel, Christoph; Roth, Joachim · In Vitro
RPEP-04940 · 2020No statistical heterogeneity in cardiovascular (MACE) or nephropathy outcomes across blood pressure categories for either liraglutide or semaglutide vs placebo.
Leiter, Lawrence A; Bain, Stephen C; Bhatt, Deepak L; Buse, John B; Mazer, C David; Pratley, Richard E; Rasmussen, Søren; Ripa, Maria Sejersten; Vrazic, Hrvoje; Verma, Subodh · Post Hoc Analysis Of RCTs
RPEP-04941 · 2020GHRH-deficient mice showed significantly increased tumor number, size, and invasiveness in a colon carcinogenesis model, with elevated COX-2, TNF-α, NF-κB, and iNOS.
Leone, Sheila; Chiavaroli, Annalisa; Recinella, Lucia; Di Valerio, Valentina; Veschi, Serena; Gasparo, Irene; Bitto, Alessandra; Ferrante, Claudio; Orlando, Giustino; Salvatori, Roberto; Brunetti, Luigi · Animal Study