RPEP-05754 · 2021LEAP2 deletion sensitized mice to ghrelin's orexigenic and GH-releasing effects, with LEAP2-KO females on high-fat diet showing 15% more body weight, 18% more food intake, 42% more hepatic fat, and increased body length.
Shankar, Kripa; Metzger, Nathan P; Singh, Omprakash; Mani, Bharath K; Osborne-Lawrence, Sherri; Varshney, Salil; Gupta, Deepali; Ogden, Sean B; Takemi, Shota; Richard, Corine P; Nandy, Karabi; Liu, Chen; Zigman, Jeffrey M · Animal Study
RPEP-05762 · 2021Intranasal oxytocin (48 IU daily for 24 weeks) showed no significant improvement in social withdrawal (ABC-mSW: -3.7 vs -3.5 placebo, p=0.61) or secondary outcomes in 290 children with autism.
Sikich, Linmarie; Kolevzon, Alexander; King, Bryan H; McDougle, Christopher J; Sanders, Kevin B; Kim, Soo-Jeong; Spanos, Marina; Chandrasekhar, Tara; Trelles, M D Pilar; Rockhill, Carol M; Palumbo, Michelle L; Witters Cundiff, Allyson; Montgomery, Alicia; Siper, Paige; Minjarez, Mendy; Nowinski, Lisa A; Marler, Sarah; Shuffrey, Lauren C; Alderman, Cheryl; Weissman, Jordana; Zappone, Brooke; Mullett, Jennifer E; Crosson, Hope; Hong, Natalie; Siecinski, Stephen K; Giamberardino, Stephanie N; Luo, Sheng; She, Lilin; Bhapkar, Manjushri; Dean, Russell; Scheer, Abby; Johnson, Jacqueline L; Gregory, Simon G; Veenstra-VanderWeele, Jeremy · Randomized Controlled Trial
RPEP-05766 · 2021Free Utorubicin was significantly more cytotoxic to cultured tumor cell lines than doxorubicin, the most widely used anthracycline in clinical oncology. When encapsulated in polymersomes (PS), UTO reduced malignant cell viability, and this effect was further enhanced by functionalization with a tumor-penetrating peptide (TPP).
In triple-negative breast cancer xenograft mice, systemic administration showed a clear hierarchy of tumor accumulation at equivalent UTO doses: TPP-targeted polymersomes > non-targeted polymersomes > free doxorubicin. The peptide-guided nanoparticles showed preferential accumulation in the tumor tissue, demonstrating successful precision delivery.
Simón-Gracia, Lorena; Sidorenko, Valeria; Uustare, Ain; Ogibalov, Ivan; Tasa, Andrus; Tshubrik, Olga; Teesalu, Tambet · Animal Study
RPEP-05770 · 2021GLP-1 receptor agonists provide comprehensive benefits in type 2 diabetes: glycemic control, weight loss, cardiovascular event reduction, nephroprotection, neuroprotection, and potential retinal protection through pleiotropic mechanisms.
Sivakumar, Ponnurengam Malliappan; Premkumar, B; Prabhawathi, Veluchamy; Prabhakar, Pranav Kumar · Review
RPEP-05771 · 2021After two-step chromatographic purification, collagen hydrolysate fractions from Clarias batrachus (C2) and Pangasius pangasius (P2) fish skin showed potent anti-inflammatory activity in LPS-activated RAW 264.7 macrophage cells. The active peptides were in the 1–3 kDa molecular weight range.
The C2 fraction reduced TNF-α gene expression to a 1.6-fold difference and IL-6 expression to a 30-fold difference compared to LPS stimulation alone. The P2 fraction reduced TNF-α to a 1.0-fold difference (essentially to baseline) and IL-6 to a 40-fold difference.
Both fractions also suppressed inflammatory proteins including TNF-α, IL-6, NFκB, and phosphorylated IκB (p-IκB), confirming the anti-inflammatory activity operates through the NFκB signaling pathway.
Sivaraman, K; Shanthi, C · In Vitro
RPEP-05776 · 2021Semaglutide's safety profile shows mainly transient GI side effects and increased cholelithiasis risk, with no unexpected safety signals across SUSTAIN and PIONEER trials and favorable cardiovascular outcomes.
Smits, Mark M; Van Raalte, Daniël H · Review
RPEP-05779 · 2021In a phase I clinical trial, a peptide vaccine based on a 9-amino acid fragment (NLVPMVATV) from CMV phosphoprotein 65 was given to 10 CMV-seronegative patients awaiting kidney transplantation. The vaccine was well tolerated with only mild local skin reactions. Five of 10 patients (50%) mounted an immune response, and 40% developed CMV-specific CD8+ T cells.
The most striking finding: none of the responders experienced CMV reactivation in the 18 months following transplantation, while all non-responders reactivated CMV. This 0% vs. 100% reactivation split, while from a tiny sample, is clinically compelling.
Sommerer, Claudia; Schmitt, Anita; Hückelhoven-Krauss, Angela; Giese, Thomas; Bruckner, Thomas; Wang, Lei; Schnitzler, Paul; Meuer, Stefan; Zeier, Martin; Schmitt, Michael · Clinical Trial
RPEP-05789 · 2021Hepatic IGF-1 mRNA was significantly lower in individuals with more severe steatosis (fat accumulation) and higher NAFLD Activity Scores, and was inversely related to blood glucose parameters independent of circulating IGF-1 levels. This means the liver's own IGF-1 production — not just what's in the blood — matters for metabolic health.
Among the binding proteins, IGFBP2 and IGFBP4 were lower while IGFBP6 and IGFBP7 were higher with increasing steatosis. Notably, IGFBP7 increased with fibrosis severity, making it a potential marker for scarring. GHRH treatment increased circulating IGFBP-1 and IGFBP-3 while decreasing IGFBP-2 and IGFBP-6, demonstrating that the GH axis can modify these binding protein profiles.
Stanley, Takara L; Fourman, Lindsay T; Zheng, Isabel; McClure, Colin M; Feldpausch, Meghan N; Torriani, Martin; Corey, Kathleen E; Chung, Raymond T; Lee, Hang; Kleiner, David E; Hadigan, Colleen M; Grinspoon, Steven K · Randomized Controlled Trial
RPEP-05790 · 2021High protein diet achieved 100% prediabetes remission vs 33% on high carb diet, with significantly greater increases in GLP-1 and GIP AUC, greater ghrelin suppression, and improved BNP over 6 months.
Stentz, Frankie B; Mikhael, Andrew; Kineish, Omer; Christman, John; Sands, Chris · Randomized Controlled Trial
RPEP-05791 · 2021Peptide-based cancer vaccines are highly specific and safe but have struggled to demonstrate clinical efficacy due to tumor heterogeneity, self-tolerance, and immune suppression. The field has responded by evolving vaccine design through multiple generations: from simple peptide derivatives to overlapping peptide libraries, conjugated peptides, targeted delivery systems, neoantigen-based personalized vaccines, and combination strategies with checkpoint inhibitors and other therapies.
The review emphasizes that effective peptide vaccines must address multiple challenges simultaneously — stimulating antigen-presenting cells, enhancing cross-presentation, breaking self-tolerance, and overcoming the immunosuppressive tumor microenvironment.
Stephens, Alexander J; Burgess-Brown, Nicola A; Jiang, Shisong · Review
RPEP-05792 · 2021Estrogen coordinates kisspeptin, POMC, and AgRP neurons through dual membrane-initiated and nuclear signaling cascades, linking reproductive control with energy homeostasis in the hypothalamus.
Stincic, Todd L; Rønnekleiv, Oline K; Kelly, Martin J · Review
RPEP-05793 · 2021IM-MS and HDX-MS detected discrete conformational states of enfuvirtide that correlate with α-helical content, with staple location dramatically altering the conformational ensemble populated by the peptide.
Stocks, Bradley B; Bird, Gregory H; Walensky, Loren D; Melanson, Jeremy E · In Vitro
RPEP-05794 · 2021At 24 hours after transient middle cerebral artery occlusion (tMCAO) in rats, Semax treatment produced measurable changes in four key brain proteins:
- **CREB** (recovery/neuroprotection): Upregulated in subcortical structures, including the ischemic damage focus
- **MMP-9** (inflammation/tissue breakdown): Downregulated in the adjacent frontoparietal cortex
- **c-Fos** (inflammatory signaling): Downregulated in the frontoparietal cortex
- **JNK** (cell death pathway): Downregulated in both subcortical structures and cortex
These protein-level changes are consistent with previous transcriptome data showing Semax suppresses inflammatory gene expression and activates neurotransmitter genes after ischemic injury.
Sudarkina, Olga Yu; Filippenkov, Ivan B; Stavchansky, Vasily V; Denisova, Alina E; Yuzhakov, Vadim V; Sevan'kaeva, Larisa E; Valieva, Liya V; Remizova, Julia A; Dmitrieva, Veronika G; Gubsky, Leonid V; Myasoedov, Nikolai F; Limborska, Svetlana A; Dergunova, Lyudmila V ·
RPEP-05796 · 2021Noodles prepared with 30% RD43 rice flour substitution significantly lowered postprandial plasma glucose at 15–90 minutes compared to control noodles. At the same time, the modified noodles significantly increased circulating levels of two key satiety peptide hormones — GLP-1 (glucagon-like peptide-1) and PYY (peptide tyrosine-tyrosine) — at 30 minutes after consumption.
Participants also reported significantly lower desire to eat and higher fullness lasting up to 120 minutes after consuming the RD43 rice noodles. The food science analysis showed that increasing RD43 rice flour content from 10–40% progressively reduced starch digestibility and rapidly digestible starch while increasing undigestible starch. Importantly, the 30% substitution level maintained similar overall sensory acceptability to conventional noodles.
Suklaew, Phim On; Chusak, Charoonsri; Wang, Chin-Kun; Adisakwattana, Sirichai · Randomized Controlled Trial
RPEP-05797 · 2021From 2,536 missense mutations in the LLC1 lung cancer cell line, researchers identified 132 candidate neoantigen peptides, of which 25 induced CD8+ T cell responses. Short peptides failed to inhibit tumor growth as vaccines, but long peptide (L82)-pulsed dendritic cells delayed tumor growth in vivo. Combining L82-pulsed DC vaccination with anti-CD38 antibody effectively suppressed tumor growth by decreasing regulatory T cells in the tumor microenvironment, converting an immunotherapy-resistant cold tumor into one susceptible to immune rejection.
Sun, Changbo; Nagaoka, Koji; Kobayashi, Yukari; Nakagawa, Hidewaki; Kakimi, Kazuhiro; Nakajima, Jun · Animal Study
RPEP-05799 · 2021CircPIP5K1A was significantly elevated in endometriosis tissues and cells. Silencing circPIP5K1A suppressed proliferation, blocked cell cycle progression, increased apoptosis, and decreased migration and invasion. The mechanism: circPIP5K1A sponges miR-153-3p, relieving its suppression of TMSB4X (Thymosin beta-4 X-linked). Elevated TMSB4X then activates TGF-β signaling, promoting endometriosis progression. Inhibiting miR-153-3p reversed the effects of circPIP5K1A knockdown, confirming the regulatory axis.
Sun, Lin; Wei, Yan; Wang, Junli · In Vitro
RPEP-05803 · 2021Gastric accommodation is the major determinant of meal volume, motilin drives return of hunger, and GLP-1/CCK/ghrelin/PYY provide hormonal gut-brain signaling for hunger and satiety regulation.
Tack, Jan; Verbeure, Wout; Mori, Hideki; Schol, Jolien; Van den Houte, Karen; Huang, I-Hsuan; Balsiger, Lukas; Broeders, Bert; Colomier, Esther; Scarpellini, Emidio; Carbone, Florencia · Review
RPEP-05807 · 2021The hybrid peptide [Lys12Pal]Ex-4/CCK demonstrated prominent insulin-releasing (insulinotropic) actions in laboratory cell tests. When administered to diabetic high-fat-fed mice with chemically damaged pancreatic beta cells for 28 days, the dual-acting peptide produced significant reductions in blood glucose levels and body weight compared to controls.
Importantly, beta-cell function markers also improved, suggesting the peptide didn't just lower blood sugar temporarily but helped protect or restore the insulin-producing cells themselves. Both exendin-4 (a GLP-1 agonist) and CCK individually showed beneficial effects on beta cells, but the combined approach in a single molecule aimed to capture synergistic benefits of activating both pathways simultaneously.
Tanday, Neil; English, Andrew; Lafferty, Ryan A; Flatt, Peter R; Irwin, Nigel · Animal
RPEP-05810 · 2021Cerebrolysin (CBL) treatment significantly improved outcomes after intracerebral hemorrhage (brain bleeding) in mice. Treated mice showed increased survival rates, better neurological scores, and greater neuron survival compared to untreated controls.
The protective mechanism involved inhibition of necroptosis — a form of programmed cell death. Cerebrolysin reduced the expression of RIP1 and RIP3 proteins, which are key drivers of necroptosis, through activation of the Akt/GSK3β signaling pathway. This suggests cerebrolysin protects brain cells not just by supporting their growth, but by actively blocking the cell death pathway that kills neurons after a brain hemorrhage.
Tao, Yunna; Xu, Yeping; Shen, Meng; Feng, Xiaoyan; Wu, Yan; Wu, Youping; Shen, Liuyan; Wang, Yuhai · Animal Study
RPEP-05814 · 2021Melittin, the primary active peptide in honeybee venom, has shown therapeutic efficacy against chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel and oxaliplatin in preclinical studies. However, melittin's clinical use has been blocked by its tendency to destroy red blood cells (hemolysis).
The authors present an original finding that α-Crystallin, an eye lens protein, can inhibit melittin-induced hemolysis. This raises the possibility that a melittin/α-Crystallin combination could deliver the neuroprotective benefits of melittin while neutralizing its most dangerous side effect.
Tender, Tenzin; Rahangdale, Rakesh Ravishankar; Balireddy, Sridevi; Nampoothiri, Madhavan; Sharma, K Krishna; Raghu Chandrashekar, Hariharapura · Review + Original Finding
RPEP-05815 · 2021The SLEEQ (Split Luciferase Endosomal Escape Quantification) assay was developed as a highly sensitive tool for quantifying cytosolic delivery of CPP-protein fusions. Testing multiple widely studied cell-penetrating peptides revealed that positively charged CPPs enhanced cytosolic delivery by increasing non-specific cell membrane association — not by improving endosomal escape efficiency.
This is a paradigm-changing finding: the field had largely assumed CPPs work by facilitating endosomal escape (helping cargo leave endosomal compartments to reach the cytosol). Instead, CPPs simply increase the total amount of cargo that associates with cells, and the same proportion escapes endosomes regardless of CPP presence.
Teo, Serena L Y; Rennick, Joshua J; Yuen, Daniel; Al-Wassiti, Hareth; Johnston, Angus P R; Pouton, Colin W · In Vitro
RPEP-05817 · 2021LC-MS/MS methods were successfully validated for ghrelin (G) and desacyl ghrelin (DAG) in plasma and urine. Limits of detection were 30-50 pg/mL with recoveries of 45-50% and imprecisions of 3-24%. Plasma quantification showed accuracies of ~100% for G and ~106% for DAG.
Healthy volunteer plasma levels ranged from 30-100 pg/mL for ghrelin and 100-1200 pg/mL for desacyl ghrelin. Critically, no endogenous ghrelin or desacyl ghrelin was detected in urine by this mass spectrometry approach, despite adequate sensitivity — contradicting earlier studies that used ligand binding assays. The method performed well at just 5% of WADA's minimum required performance level of 2 ng/mL in urine.
Thomas, Andreas; Krombholz, Sophia; Wolf, Carina; Thevis, Mario · Methods
RPEP-05821 · 2021All four chirally tuned tripeptide hydrogels formed mechanoresponsive (self-healing) nanofibrillar networks under physiological conditions. The gels demonstrated antimicrobial activity against both Gram-positive bacteria (Staphylococcus aureus and Streptococcus mutans) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia).
Critically, the hydrogels were biocompatible with mammalian cells as confirmed by MTT viability assays, hemolysis tests, and lipid peroxidation assays. Anti-inflammatory activity was validated through MMP2/MMP9 inhibition studies in vitro and a rat pouch model for acute inflammation in vivo. The inclusion of D-amino acids at specific positions allowed fine-tuning of the gels' mechanical strength.
Tiwari, Priyanka; Gupta, Arindam; Shukla, Durgesh Nandan; Mishra, Ankit K; Basu, Anindya; Dutt Konar, Anita · Animal
RPEP-05823 · 2021GLP-1RA reduced allergen-induced airway neutrophilia and multiple inflammatory cytokines in obese mice, an effect not achieved by TSLP or ST2 inhibition alone.
Toki, Shinji; Newcomb, Dawn C; Printz, Richard L; Cahill, Katherine N; Boyd, Kelli L; Niswender, Kevin D; Peebles, R Stokes · Animal
RPEP-05825 · 2021The review identifies seven constitutive respiratory defense barriers against SARS-CoV-2:
1. Mucus and mucociliary clearance
2. Surfactants (inhibit viral invasion, enhance phagocytosis)
3. Respiratory microbiota (activates immune cells, induces defensins and IgA)
4. Antimicrobial peptides — defensins and lactoferrin (direct antiviral activity, inhibit viral fusion, modulate immunity)
5. Secretory IgA antibodies (inhibit viral cell invasion)
6. Respiratory epithelial cells (restrict receptor access, produce interferons, lactoferrin, defensins)
7. Innate immune cell sensing (triggers adaptive immunity cascade)
Antimicrobial peptides feature prominently in barriers 4 and 6, highlighting their central role in respiratory defense.
Tosta, Eduardo · Review
RPEP-05829 · 2021Starting from earlier lead compounds, the researchers optimized a series of bi- and tricyclic peptide structures to create compound 44, which demonstrated sufficient oral bioavailability in both rats and cynomolgus monkeys to maintain therapeutic blood levels using an enabled formulation.
When tested in monkeys, the optimized peptides achieved target engagement and LDL cholesterol lowering essentially identical to the clinically approved injectable PCSK9 antibodies (evolocumab and alirocumab). This represents the first demonstration that macrocyclic peptides can match antibody-level efficacy through oral delivery for this target.
Tucker, Thomas J; Embrey, Mark W; Alleyne, Candice; Amin, Rupesh P; Bass, Alan; Bhatt, Bhavana; Bianchi, Elisabetta; Branca, Danila; Bueters, Tjerk; Buist, Nicole; Ha, Sookhee N; Hafey, Mike; He, Huaibing; Higgins, John; Johns, Douglas G; Kerekes, Angela D; Koeplinger, Kenneth A; Kuethe, Jeffrey T; Li, Nianyu; Murphy, BethAnn; Orth, Peter; Salowe, Scott; Shahripour, Aurash; Tracy, Rodger; Wang, Weixun; Wu, Chengwei; Xiong, Yusheng; Zokian, Hratch J; Wood, Harold B; Walji, Abbas · Animal
RPEP-05841 · 2021The review identifies three primary barriers to oral peptide/protein delivery:
1. Acid degradation in the stomach (pH 1-2)
2. Enzymatic degradation by proteases throughout the GI tract
3. Poor cellular membrane permeability at the intestinal absorption site, plus first-pass hepatic metabolism
Current strategies to overcome these barriers include:
- Absorption enhancers and carriers to improve gut permeability
- Structural modifications (cyclization, D-amino acid substitution, PEGylation) to improve stability
- Advanced formulation technologies (nanoparticles, liposomes, microspheres)
- Enzyme inhibitors to protect against proteolytic degradation
- Enteric coatings to bypass stomach acid
Verma, Saurabh; Goand, Umesh K; Husain, Athar; Katekar, Roshan A; Garg, Richa; Gayen, Jiaur R · Review
RPEP-05842 · 2021Semaglutide reduced MACE by 26% (HR 0.74) in patients with established CVD using REWIND criteria, with a non-significant 16% reduction in the risk factor subgroup (p-interaction=0.60).
Verma, Subodh; Fainberg, Udi; Husain, Mansoor; Rasmussen, Søren; Rydén, Lars; Ripa, Maria Sejersten; Buse, John B · Clinical Trial
RPEP-05852 · 2021RNA sequencing of skin from six rosacea patients identified 237 differentially expressed long non-coding RNAs, 38 miRNAs, and 1,784 mRNAs in lesioned vs. non-lesioned skin. NEAT1 was upregulated in both rosacea skin tissue and LL-37-treated HaCaT cells. Knocking down NEAT1 reduced inflammatory damage in vitro. NEAT1 directly interacted with miR-196a-5p, and downregulating miR-196a-5p reversed the anti-inflammatory effects of NEAT1 knockdown on S100A9, confirming the NEAT1/miR-196a-5p/S100A9 regulatory axis.
Wang, Lian; Wang, Yu-Jia; Hao, Dan; Wang, Xiao-Yun; Li, Xiao-Xue; Zhao, Qian; Li, Yan-Mei; He, Gu; Jiang, Xian ·
RPEP-05854 · 2021Diphenylalanine (FF) dipeptides modified with three different aromatic groups (benzene, naphthalene, pyrene) all formed composite hydrogels with hyaluronic acid (HA) featuring uniform distribution and good mechanical properties.
The naphthalene-modified version (N-FF/HA) showed the best performance: excellent self-healing properties (reforming after injection through a syringe), good biocompatibility with human skin fibroblast cells, and a structure of thinner nanofibers with honeycomb networks that enabled sustained curcumin release. In a streptozotocin-induced type I diabetic mouse model, curcumin-loaded N-FF/HA composite hydrogels promoted chronic wound healing significantly better than controls.
Wang, Ling; Li, Jing; Xiong, Yue; Wu, Yihang; Yang, Fen; Guo, Ying; Chen, Zhaolin; Gao, Liqian; Deng, Wenbin ·
RPEP-05857 · 2021Substance P (50 mg/ml/kg, intraperitoneal) administered before fracture surgery in type 1 diabetic rats promoted bone healing through multiple measured effects: upregulation of osteogenic markers RUNX2, osterix (OSTX), and osteocalcin (OSTC); optimization of the bone resorption axis with favorable OPG/RANKL/RANK balance; and activation of the Wnt/β-catenin signaling pathway manifested by upregulated β-catenin and LRP5 with downregulated GSK-3β.
Critically, local delivery of the Wnt antagonist DKK1 (via adenovirus) at the fracture site reversed substance P's beneficial effects, confirming that the Wnt/β-catenin pathway is the essential mediator. Radiographic assessment showed reduced gap size in substance P-treated diabetic fractures compared to untreated diabetic fractures.
Wang, Xiaohui; Su, Ning ·
RPEP-05858 · 2021All four CGRP monoclonal antibodies significantly reduced monthly migraine days (MMDs) compared to placebo: eptinezumab (MD -1.43 days), erenumab (MD -1.61 days), fremanezumab (MD -2.19 days), and galcanezumab (MD -2.10 days).
Regarding safety, only galcanezumab showed significantly increased treatment-emergent adverse events (RR 1.11, 95% CrI 1.01–1.22) and serious adverse events (RR 2.95, 95% CrI 1.41–6.87) compared to placebo. The other three antibodies had adverse event rates comparable to placebo. Overall, the drugs performed similarly to each other across most analyses.
Wang, Xing; Chen, Yuqi; Song, Jinlei; You, Chao ·
RPEP-05865 · 2021Adding thymosin beta-4 (Tβ4) to ciprofloxacin antibiotic treatment significantly improved outcomes in bacterial eye infections in mice. The combination reduced the number of neutrophils (PMNs) infiltrating infected corneas and downregulated pro-inflammatory markers on those cells. Tβ4 also promoted well-regulated production of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs), with limited neutrophil death (apoptosis).
The study confirmed both in vivo and in vitro that Tβ4 modulates how neutrophils respond to infection — not by suppressing immunity, but by regulating it. An additional finding was that neutrophil elastase (NE) was unnecessary for NET formation (NETosis), challenging previous assumptions about how NETs are generated.
Wang, Yuxin; Carion, Thomas W; Ebrahim, Abdul Shukkur; Sosne, Gabriel; Berger, Elizabeth A · Animal Study
RPEP-05867 · 2021Among 275 COVID-19 patients (126 receiving Tα1, 149 not), there was no significant difference in CD4+ T cell recovery (286 vs. 326, p=0.851) or CD8+ T cell recovery (154 vs. 170, p=0.842) during the recovery period.
Notably, in patients with decreased baseline CD4 counts and in the severe illness subgroup, virus clearance duration was significantly longer in the Tα1-treated group. Multivariate regression analysis confirmed that both illness severity (p<0.001) and Tα1 therapy (p=0.001) were independently associated with virus clearance time — with Tα1 therapy associated with longer clearance.
Wang, Zhenyan; Chen, Jun; Zhu, Cuiyun; Liu, Li; Qi, Tangkai; Shen, Yinzhong; Zhang, Yuyi; Xu, Lie; Li, Tao; Qian, Zhiping; Steinhart, Corklin R; Lu, Hongzhou ·
RPEP-05868 · 2021Researchers successfully created transgenic rats where vasopressin-producing neurons in specific brain regions (PVN and SON) could be selectively destroyed using diphtheria toxin. When these neurons were ablated, rats developed excessive thirst and urination — symptoms that were rescued by administering the vasopressin analog DDAVP (desmopressin) via an osmotic mini-pump.
Importantly, the technique selectively targeted vasopressin neurons without affecting neighboring oxytocin-producing neurons, and neurons in the suprachiasmatic nucleus (SCN) were spared, demonstrating regional specificity.
Watanabe, Jun; Takayanagi, Yuki; Yoshida, Masahide; Hattori, Tatsuya; Saito, Michiko; Kohno, Kenji; Kobayashi, Eiji; Onaka, Tatsushi ·
RPEP-05877 · 2021Acute high-intensity exercise increases concentrations of the mitochondrial-derived peptides (MDPs) humanin and MOTS-c in human skeletal muscle and plasma. MOTS-c treatment in mice improved exercise capacity and performance in both young and aged animals, producing adaptations similar to physical activity — including weight loss, increased antioxidant capacity, and improved insulin sensitivity. However, studies using a MOTS-c inactivating genetic variant and combination exercise + MOTS-c treatment suggest distinct and overlapping pathways between exercise and MOTS-c benefits. Evidence for chronic training effects on MDP expression is conflicting and appears to depend on exercise mode, duration, intensity, and participant characteristics.
Woodhead, Jonathan S T; Merry, Troy L ·
RPEP-05883 · 2021LL-37 and lactoferricin enhanced the anti-biofilm effect of amoxicillin and clindamycin in facultative anaerobic biofilms (S. mutans, S. sanguinis, A. naeslundii). Metronidazole, which was ineffective alone against these biofilms, showed significant biofilm reduction when combined with either peptide.
Obligate anaerobic biofilms (V. parvula, P. micra, F. nucleatum) showed enhanced tolerance to amoxicillin and clindamycin, likely due to metabolic downshifts. However, combining these antibiotics with LL-37 or lactoferricin markedly enhanced biofilm reduction for all three antibiotics. The peptides also appeared to promote dispersion of mature biofilms, suggesting a mechanism for overcoming biofilm-mediated antibiotic tolerance.
Wuersching, Sabina Noreen; Huth, Karin Christine; Hickel, Reinhard; Kollmuss, Maximilian ·
RPEP-05886 · 2021Cy5p53Tet — a p53 tetramerization domain peptide conjugated to Cy5 fluorophore — showed higher nuclear uptake in TNBC MDA-MB-468 cells (with mutant p53 R273H) versus ER-positive MCF7 cells (with wild-type p53) by confocal microscopy and flow cytometry. Depletion of mutant p53 reduced peptide uptake, confirming target specificity. In mice bearing xenografts, Cy5p53Tet was detectable in tumor tissue within 12 minutes of injection. Significantly higher uptake was observed in mutant p53-expressing TNBC tumors compared to wild-type p53 tumors.
Xiao, Gu; Annor, George K; Fung, Kimberly; Keinänen, Outi; Zeglis, Brian M; Bargonetti, Jill ·
RPEP-05892 · 2021Two nonameric peptides (Peptide32-40 and Peptide175-183) identified from canine MMP-7 via immunoinformatics induced significant lymphocyte proliferation and IFN-γ production from CD8+ T cells in BALB/c mice immunized with a cMMP-7 DNA vaccine.
The DNA vaccine itself triggered strong CD8+ cytotoxic T lymphocyte (CTL) and Th1-type responses with high IFN-γ levels. The cross-species (xenovaccine) approach — using canine MMP-7 in mice — successfully overcame the immunological tolerance that typically limits vaccines targeting endogenous tumor-associated antigens.
Yadav, Pavan Kumar; Gupta, Shishir Kumar; Kumar, Saroj; Ghosh, Mayukh; Yadav, Brijesh Singh; Kumar, Dinesh; Kumar, Ajay; Saini, Mohini; Kataria, Meena ·
RPEP-05896 · 2021When added to the nicotine patch, exenatide (a GLP-1 receptor agonist) nearly doubled smoking quit rates: 46.3% of the exenatide group achieved abstinence versus 26.8% on placebo (risk ratio 1.70, posterior probability 96.5%). Exenatide also reduced cravings in the overall sample and withdrawal symptoms among those who quit.
Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (posterior probability 97.4%), addressing one of the most common barriers to quitting — weight gain. Adverse events were higher in the exenatide group (9.5% vs 2.3%) but the treatment was generally tolerable.
Yammine, Luba; Green, Charles E; Kosten, Thomas R; de Dios, Constanza; Suchting, Robert; Lane, Scott D; Verrico, Christopher D; Schmitz, Joy M · Randomized Controlled Trial
RPEP-05897 · 2021The HTLAC nanosystem demonstrated dual theranostic (therapy + diagnostic) function:
- In the presence of DT-diaphorase (overexpressed in tumors), the system simultaneously released withaferin A (anti-cancer) and activated the fluorescent probe DT-Cy5 (for tumor imaging)
- Both enzyme-triggered reactions generated reactive oxygen species, and withaferin A itself produces additional intracellular ROS, creating a self-amplifying 'ROS burst'
- Cell-penetrating peptide enhanced cellular uptake while hyaluronic acid provided active tumor targeting and prolonged blood circulation
- In vitro and in vivo studies showed enhanced tumor detection, superior antitumor efficiency, and low systemic toxicity
Yan, Dan; Xu, Xiao; Ren, Chunling; Chen, Chen; Luo, Jianguang; Han, Chao; Kong, Lingyi ·
RPEP-05901 · 2021The review identifies multiple potential benefits of GLP-1 receptor agonists in sepsis: regulation of blood glucose homeostasis (addressing stress hyperglycemia), improvement of organ dysfunction, modulation of immune responses, and control of inflammation. These properties suggest GLP-1RAs could serve as a new therapeutic approach for sepsis, particularly in patients with stress hyperglycemia — a common and dangerous complication.
Yang, Fuxun; Zeng, Fan; Luo, Xiaoxiu; Lei, Yu; Li, Jiajia; Lu, Sen; Huang, Xiaobo; Lan, Yunping; Liu, Rongan ·
RPEP-05909 · 2021CPPs improve endosomal escape and mRNA delivery efficiency, particularly to dendritic cells.
Yokoo, Hidetomo; Oba, Makoto; Uchida, Satoshi ·
RPEP-05910 · 2021This minireview surveys strategies for creating antimicrobial peptide (AMP) foldamers — synthetic peptide-like molecules that use non-natural amino acids to adopt stable helical structures. The approaches discussed include incorporating α,α-disubstituted amino acids, β-amino acids, γ-amino acids, side-chain stapling, and N-alkyl glycines. These modifications help AMPs maintain their membrane-disrupting amphipathic structure while potentially improving stability against enzymatic degradation and enhancing antimicrobial activity.
Yokoo, Hidetomo; Hirano, Motoharu; Misawa, Takashi; Demizu, Yosuke · Review
RPEP-05915 · 2021Researchers engineered a four-module chimeric peptide system that solves two major problems with cell-penetrating peptide drug delivery: poor endosomal escape (cargo gets trapped inside cellular compartments) and degradation in blood serum.
The system chains together: (1) a cell-penetrating peptide to enter cells, (2) a pH-sensitive membrane-active peptide that activates in acidic endosomes, (3) protease cleavage sites that release cargo when cut by endosome-specific enzymes, and (4) a leucine zipper that dimerizes the construct for enhanced function. When used to deliver the therapeutic protein phosphatase 1B (PTP1B) intravenously in mice, it successfully suppressed TNF-α-induced systemic inflammation and prevented acetaminophen-induced acute liver failure.
Yu, Siyuan; Yang, Han; Li, Tingdong; Pan, Haifeng; Ren, Shuling; Luo, Guoxing; Jiang, Jinlu; Yu, Linqi; Chen, Binbing; Zhang, Yali; Wang, Shaojuan; Tian, Rui; Zhang, Tianying; Zhang, Shiyin; Chen, Yixin; Yuan, Quan; Ge, Shengxiang; Zhang, Jun; Xia, Ningshao · Preclinical
RPEP-05917 · 2021Ghrelin, a 28-amino-acid peptide from the stomach, has multiple cardioprotective effects beyond its well-known role in appetite and growth hormone. Research shows ghrelin modulates sympathetic nervous system activity and blood pressure, enhances blood vessel function and new vessel growth (angiogenesis), inhibits cardiac arrhythmias, reduces heart failure progression, and inhibits harmful cardiac remodeling after heart attacks.
The underlying mechanisms include anti-inflammatory effects, prevention of cell death (anti-apoptosis), suppression of sympathetic nerve overactivation, regulation of autophagy, and correction of endothelial dysfunction. However, the molecular details remain incompletely understood and no ghrelin-based cardiovascular drug exists yet.
Yuan, Ming-Jie; Li, Wei; Zhong, Peng · Review
RPEP-05919 · 2021Peptide therapeutics entering clinical development have increased significantly over the past decade, but regulatory frameworks haven't kept pace. A key challenge: existing FDA/ICH guidelines (ICH M3(R2) for small molecules and ICH S6(R1) for biologics) were not designed for peptides, which fall somewhere in between. Regulators and drug companies interpret these guidelines differently for synthetic and conjugated peptides, creating inconsistency in nonclinical testing requirements.
The symposium addressed four specific challenges: (1) discovery and optimization of combination peptide therapeutics, (2) toxicological requirements for peptide drug-device combination products (like auto-injectors), (3) regulatory classification disputes — are synthetic peptides drugs or biologics? — and (4) genotoxicity testing requirements, which may be unnecessary for many peptides but are still often required.
Zane, Doris; Feldman, Paul L; Sawyer, Tomi; Sobol, Zhanna; Hawes, Jessica · Review
RPEP-05921 · 2021Participants taking collagen peptides experienced a 21.9 mm reduction on the Visual Analog Scale (VAS) for exercise-induced knee pain, compared to 15.6 mm for placebo (p = 0.024). Physician evaluations showed an even clearer difference: 23.0 mm reduction versus 14.6 mm (p = 0.003).
Pain at rest and after performing 20 squats did not differ significantly between groups, but this was largely because few participants had pain under those conditions at baseline. Joint mobility was clinically unremarkable at the start and remained unchanged.
Zdzieblik, Denise; Brame, Judith; Oesser, Steffen; Gollhofer, Albert; König, Daniel ·
RPEP-05926 · 2021Macrocycle 6 selectively inhibits Mtb20S, leading to the death of nonreplicating Mtb.
Zhang, Hao; Hsu, Hao-Chi; Kahne, Shoshanna C; Hara, Ryoma; Zhan, Wenhu; Jiang, Xiuju; Burns-Huang, Kristin; Ouellette, Tierra; Imaeda, Toshihiro; Okamoto, Rei; Kawasaki, Masanori; Michino, Mayako; Wong, Tzu-Tshin; Toita, Akinori; Yukawa, Takafumi; Moraca, Francesca; Vendome, Jeremie; Saha, Priya; Sato, Kenjiro; Aso, Kazuyoshi; Ginn, John; Meinke, Peter T; Foley, Michael; Nathan, Carl F; Darwin, K Heran; Li, Huilin; Lin, Gang ·
RPEP-05927 · 2021Among 191 sepsis patients divided into Tβ4 concentration tertiles (1.19–7.11, 7.12–11.01, and 11.02–28.10 ng/ml), lower Tβ4 was significantly associated with worse outcomes:
- Acute kidney injury: OR 2.102 per stage lower (95% CI 1.448–3.050, p<0.001)
- Need for continuous renal replacement therapy: OR 2.346 per stage lower (95% CI 1.287–4.276, p=0.005)
- 7-day mortality: OR 1.755 per stage lower (95% CI 1.050–2.935, p=0.032)
- 28-day mortality: OR 1.821 per stage lower (95% CI 1.209–2.743, p=0.004)
The predictive accuracy (AUC) for each outcome ranged from 0.682 to 0.717. Kaplan-Meier analysis confirmed that patients in lower Tβ4 tertiles had significantly higher cumulative risks of AKI and death.
Zhang, Jiahao; Long, Minghui; Sun, Zhongyi; Yang, Cheng; Jiang, Xiaofang; He, Li; Su, Lianjiu; Peng, Zhiyong ·