RPEP-06187 · 2022DNA mismatch repair-deficient cancers produce a defined and predictable set of frameshift peptide neoantigens due to insertion/deletion mutations in coding microsatellites. These neoantigens are foreign to the immune system and can elicit strong CD8+ cytotoxic T cell responses.
Evidence shows pre-existing immune surveillance against these neoantigens exists in Lynch syndrome carriers, suggesting the immune system already partially recognizes pre-cancerous cells. Three mechanisms of immune evasion allow cancers to escape this surveillance. A preventive vaccine could strengthen immune surveillance before evasion occurs. The review evaluates antigen selection and delivery strategies, concluding that RNA vaccines offer the most robust potential for immunoprevention.
Hernandez-Sanchez, Alejandro; Grossman, Mark; Yeung, Kevin; Sei, Shizuko S; Lipkin, Steven; Kloor, Matthias ·
RPEP-06190 · 2022The review maps the four endogenous opioid peptide systems and their roles:
1. μ-opioid receptor (MOPR) / β-endorphins — primary mediator of pain relief and euphoria; the main target of opioid drugs
2. κ-opioid receptor (KOPR) / dynorphins — involved in stress responses and dysphoria; may contribute to negative emotional states during withdrawal
3. δ-opioid receptor (DOPR) / enkephalins — modulates mood, motivation, and pain; potential target for non-addictive analgesics
4. Nociceptin receptor (NOPR) / nociceptins — regulates pain sensitivity, anxiety, and stress responses
Key insight: chronic pain itself alters endogenous opioid system function, and these alterations — combined with the effects of exogenous opioid use — create a self-reinforcing cycle that increases the likelihood of developing opioid use disorder.
Higginbotham, Jessica A; Markovic, Tamara; Massaly, Nicolas; Morón, Jose A ·
RPEP-06192 · 2022PRRT with 177Lu-DOTATATE (approved 2017-2018) is an established treatment for somatostatin receptor-positive well-differentiated neuroendocrine neoplasms (NENs):
- Improves progression-free survival and quality of life in GEP NEN patients
- Shows favorable symptomatic and biochemical responses in functioning metastatic tumors including insulinomas, VIPomas, glucagonomas, and gastrinomas
- Being investigated as first-line therapy and in combination with cytotoxic drugs
- Expanding to bronchopulmonary NENs, pheochromocytomas, paragangliomas, and medullary thyroid carcinomas
Next-generation developments include somatostatin analog peptides coupled with alpha-emitting radionuclides (more potent radiation) and somatostatin receptor antagonists with radionuclides.
Hofland, Johannes; Brabander, Tessa; Verburg, Frederik A; Feelders, Richard A; de Herder, Wouter W ·
RPEP-06193 · 2022Five patients with high-risk MDS who had previously responded to azacitidine (AZA) monotherapy received a multi-peptide vaccine targeting NY-ESO-1, MAGE-A3, PRAME, and WT-1 antigens.
Results were uniformly negative: no specific immune responses were detected by intracellular cytokine staining or ELISpot assays. Only minor changes in immune cell phenotype and marker expression were observed. All five patients progressed to acute myeloid leukemia (AML) with a mean time to progression of 5.2 months (range 2.8-7.6). Mean survival was 18.1 months from MDS diagnosis (range 10.9-30.6) and 11.3 months from study enrollment (range 4.3-22.2). Bone marrow sequencing revealed clonal expansion of malignant cells and emergence of novel mutations.
Holmberg-Thydén, Staffan; Dufva, Inge Høgh; Gang, Anne Ortved; Breinholt, Marie Fredslund; Schejbel, Lone; Andersen, Mette Klarskov; Kadivar, Mohammad; Svane, Inge Marie; Grønbæk, Kirsten; Hadrup, Sine Reker; El Fassi, Daniel ·
RPEP-06197 · 2022The evidence for natriuretic peptide-guided therapy splits along several lines. In heart failure with reduced ejection fraction (HFrEF), the STARS-BNP and PROTECT trials demonstrated reduced cardiac events when medications were adjusted based on NP levels. Meta-analyses and the BATTLESCARRED and TIME-CHF studies showed mortality reduction specifically in patients under 75 years old.
However, the PRIMA and GUIDE-IT trials found no significant differences between NP-guided and conventional care. In heart failure with preserved ejection fraction (HFpEF) and in acute heart failure settings, NP-guided therapy showed no benefit over standard care. A promising application is in prevention: NP levels may help identify people at risk of developing heart failure and guide early intervention.
Horiuchi, Yu; Villacorta, Humberto; Maisel, Alan S ·
RPEP-06205 · 2022Self-assembling peptides (SAPs) were grafted onto O-carboxymethyl chitosan (O-CMCS) to create a hydrogel with sustained-release properties for both mel-d1 (a modified melittin antimicrobial peptide with reduced cytotoxicity) and ciprofloxacin. The drug retention was enhanced by hydrophobic interactions and π-π stacking between the scaffold and the drugs. In vivo, the dual-loaded hydrogel accelerated wound closure and skin tissue regeneration in E. coli-infected mouse wounds. The SAP component itself contributed to tissue healing beyond its role as a drug carrier.
Huan, Yuchen; Kong, Qing; Tang, Qingjuan; Wang, Yuming; Mou, Haijin; Ying, Rui; Li, Chunjun ·
RPEP-06206 · 2022Oral BPC 157 reduced radiation-induced liver injury in mice irradiated with 12 Gy. Specifically, it lowered plasma AST and ALT levels (liver damage markers), inhibited hydropic degeneration of liver tissue, and significantly decreased radiation-induced cell death (apoptosis).
BPC 157 increased PCNA expression (a marker of cell proliferation), promoted KLF4 expression, reduced hepatic lipid accumulation, and decreased HIF-2α expression in both mouse liver tissue and cultured rat liver cells. The critical finding: when KLF4 was knocked down using siRNA, BPC 157's protective effects on apoptosis and lipid accumulation were abolished — proving that KLF4 mediates BPC 157's liver-protective mechanism.
Huang, Bing-Shen; Huang, Shih-Chiang; Chen, Fang-Hsin; Chang, Yu; Mei, Hsiu-Fu; Huang, Hsiu-Yun; Chen, Wan-Yu; Pang, Jong-Hwei Su ·
RPEP-06211 · 2022Dyskinesia severity correlated with levels of abnormally processed peptides — des-tyrosine dynorphins, substance P (1-7), and substance P (1-9) — across multiple brain regions. Active neuropeptides (dynorphin B, dynorphin A (1-8), α-neoendorphin, substance P (1-11), neurokinin A) in the globus pallidus and substantia nigra correlated with putaminal L-DOPA concentrations. Truncated neuropeptides with reduced or altered receptor affinity correlated specifically with dyskinesia severity, particularly those in the direct pathway (dynorphins and tachykinins). The findings suggest increased neuropeptide tone in LID leads to abnormal processing as a compensatory mechanism.
Hulme, Heather; Fridjonsdottir, Elva; Vallianatou, Theodosia; Shariatgorji, Reza; Nilsson, Anna; Li, Qin; Bezard, Erwan; Andrén, Per E ·
RPEP-06213 · 2022Various peptides isolated from venomous animals (spiders, scorpions, and others) can potently and selectively bind to the outer pore region of the TRPV1 ion channel — a key pain receptor. These venom peptides can either activate or inhibit TRPV1, and their specificity for this particular region of the receptor makes them valuable templates for designing new pain medications.
TRPV1 is activated by multiple painful stimuli including heat, acid, and inflammatory chemicals, and contributes to both acute and chronic pain conditions. By targeting its outer pore rather than its ligand-binding site, venom peptides offer a mechanistically distinct approach to controlling pain signaling.
Hwang, Sung-Min; Jo, Youn-Yi; Cohen, Cinder Faith; Kim, Yong-Ho; Berta, Temugin; Park, Chul-Kyu · Review
RPEP-06215 · 2022In 80 chronic migraine patients who responded well to anti-CGRP antibodies (erenumab, fremanezumab, or galcanezumab), the drugs prevented not just the headache but also the anticipatory and accompanying symptoms of migraine. Most patients experienced complete prevention without evidence of an attack starting and being aborted. Only 10–12.5% reported residual prodromal symptoms without headache, and 1.3–8.8% had accompanying symptoms without headache. All patients with aura reported decreased aura incidence. Additional effects included sleep changes (51.2%), increased appetite (20%), weight gain (18.8%), reduced stress (45%), reduced anxiety (26.3%), and fewer panic attacks (15%).
Iannone, Luigi Francesco; De Cesaris, Francesco; Ferrari, Anita; Benemei, Silvia; Fattori, Davide; Chiarugi, Alberto ·
RPEP-06216 · 2022All three anti-CGRP monoclonal antibodies showed similar effectiveness in this treatment-resistant population, with only 17.2% of patients dropping out over the study period.
Using the MIDAS disability score, 89.5–100% of patients achieved at least 50% reduction at various follow-up points, and 84.4–100% maintained this at 12 months. By comparison, the traditional ≥50% reduction in monthly migraine days was achieved by only 36.4–66.6% of patients — substantially lower.
This discrepancy suggests that MIDAS captures functional improvements (less disability per migraine day, better coping) that raw migraine day counts miss. Monthly analgesic use also decreased substantially, with 51.1–75.7% achieving ≥50% reduction.
84.7% of enrolled patients also had medication overuse at baseline. No severe adverse events were recorded. Fewer baseline migraine days predicted better early response.
Iannone, Luigi Francesco; Fattori, Davide; Benemei, Silvia; Chiarugi, Alberto; Geppetti, Pierangelo; De Cesaris, Francesco ·
RPEP-06217 · 2022Of the defensin genes expressed in the nasopharyngeal/oropharyngeal cavity, nine were detected by qRT-PCR analysis. Four defensin genes were significantly downregulated in SARS-CoV-2-infected patients compared to controls: defensin beta 4A/B (encoding human beta-defensin 2), 106B (beta-defensin 6), 107B (beta-defensin 7), and 103A (beta-defensin 3).
These beta-defensins are known to have antiviral properties, and their suppression during infection suggests that SARS-CoV-2 may compromise the innate immune peptide defense system. The authors propose that defensin peptide-based therapy could be explored as a treatment approach to correct this immune suppression.
Idris, Mohammed M; Banu, Sarena; Siva, Archana B; Nagaraj, Ramakrishnan ·
RPEP-06219 · 2022Human periodontal ligament fibroblasts (PDLFs) constitutively express the fungal pattern recognition receptor Dectin-1. Stimulation with zymosan (β-glucan-rich fungal component) induced expression of cytokines IL-6, IL-1β, and IL-17A, chemokine IL-8, and the antimicrobial peptide β-defensin-1 (DEFB1), along with phosphorylation of Syk and NF-κB.
Heat-killed Candida albicans similarly induced IL-6, IL-17A, IL-8, and DEFB1 expression in PDLFs, and this response was suppressed by the Syk inhibitor R406 — confirming the Dectin-1/Syk pathway as the specific mechanism. This demonstrates that gum tissue fibroblasts are active participants in antifungal innate immunity, not just structural support cells.
Inomata, Megumi; Amano, Shigeru; Abe, Masayo; Hayashi, Toru; Sakagami, Hiroshi ·
RPEP-06223 · 2022Key findings from this phage display-based peptide discovery:
- A disulfide-bridged cyclic heptapeptide was identified that binds CsrA from Yersinia pseudotuberculosis and displaces bound RNA
- IC50 in the low micromolar range
- Cyclization was essential — linear versions lost activity
- A redox-stable triazole analogue (replacing the disulfide bridge) showed activity in the double-digit micromolar range with improved metabolic stability
- The triazole peptidomimetic was also active against:
- CsrA from Escherichia coli
- RsmA from Pseudomonas aeruginosa
- This demonstrates broad-spectrum anti-virulence potential across multiple pathogenic species
Jakob, Valentin; Zoller, Ben G E; Rinkes, Julia; Wu, Yingwen; Kiefer, Alexander F; Hust, Michael; Polten, Saskia; White, Andrew M; Harvey, Peta J; Durek, Thomas; Craik, David J; Siebert, Andreas; Kazmaier, Uli; Empting, Martin ·
RPEP-06224 · 2022Tirzepatide, a dual GIP/GLP-1 receptor agonist, produced dose-dependent weight loss that far exceeded placebo in adults with obesity but without diabetes. At week 72, mean weight loss was 15.0% with 5 mg, 19.5% with 10 mg, and 20.9% with 15 mg, compared to just 3.1% with placebo (P<0.001 for all comparisons).
At the highest dose, 91% of participants lost at least 5% of their body weight and 57% lost at least 20% — a threshold previously achievable mainly through bariatric surgery. Improvements were observed across all prespecified cardiometabolic measures. Gastrointestinal side effects were the most common but were predominantly mild to moderate and occurred primarily during the 20-week dose-escalation period.
Jastreboff, Ania M; Aronne, Louis J; Ahmad, Nadia N; Wharton, Sean; Connery, Lisa; Alves, Breno; Kiyosue, Arihiro; Zhang, Shuyu; Liu, Bing; Bunck, Mathijs C; Stefanski, Adam ·
RPEP-06236 · 2022The vaccine induced robust CD8+ T cell responses and achieved complete tumor clearance in multiple models.
Jing, Zhe; Wang, Shuqing; Xu, Keyuan; Tang, Qian; Li, Wenjing; Zheng, Wei; Shi, Haobo; Su, Kailing; Liu, Yanting; Hong, Zhangyong ·
RPEP-06239 · 2022The melittin-derived peptide P1 (sequence TTGLPALISWIKRKRQQ) maintained anti-inflammatory effects comparable to melittin, including inhibition of inflammatory cytokine mRNA expression and IκBα phosphorylation in RAW 264.7 macrophage cells. P1 also showed antioxidant activity comparable to full-length melittin in ABTS radical scavenging assays.
Critically, P1 showed negligible cytotoxicity in MTS assays (unlike melittin's high toxicity) and remarkably reduced allergenicity compared to melittin, as measured by β-hexosaminidase release from RBL-2H3 mast cells. This separation of therapeutic activity from toxic side effects represents a significant advance in bee venom peptide engineering.
Jung, Haesoo; Kim, Yong Soo; Jung, Da-Min; Lee, Kyeong-Seob; Lee, Jung-Min; Kim, Kee K ·
RPEP-06243 · 2022Children with active celiac disease had significantly elevated fecal β-defensin-2 levels (99.6 vs 64.0 ng/mL, p<0.001) and higher anti-BPI antibodies compared to healthy controls. Fecal calprotectin and β-defensin-2 were moderately correlated (r=0.69), and β-defensin-2 weakly correlated with anti-BPI antibodies (r=0.35). These findings suggest that antimicrobial peptides are part of the gut's innate immune response in celiac disease.
Kamilova, Altinoy T; Azizova, Gulnoza K; Umarnazarova, Zulkhumar E; Abdullaeva, Dilrabo A; Geller, Svetlana I · Case Control
RPEP-06253 · 2022Biocompatible microneedles made of sodium hyaluronate successfully collected skin specimens from 33 subjects for full transcriptome analysis. The researchers identified specific gene biomarkers correlating with five skin conditions: COL1A1, FN1, and PINK1 for skin aging; FLG, KLF4, and LOR for hydration; GPNMB, MLANA, and TYR for pigmentation; IGF1, MPZL3, and AQP3 for oily skin; and PGF, CYR61, RBP4, TAC1, CAMP (cathelicidin antimicrobial peptide), MMP9, MMP3, MMP12, and CCR1 for sensitive skin. The biomarkers correlated with age, device measurements, lactic acid stinging test scores, and visual assessments.
Kim, Seo Hyeong; Kim, Ji Hye; Lee, Sung Jae; Jung, Min Sook; Jeong, Do Hyeon; Lee, Kwang Hoon ·
RPEP-06267 · 2022Two JR11 analogs (8a and 8b) carrying albumin-binding domains were synthesized and labeled with lutetium-177 for radionuclide therapy evaluation:
- Both achieved >97% radiochemical purity and >95% stability in PBS and mouse serum
- 8a showed better human albumin binding affinity than 8b
- Both analogs had significantly lower SSTR2 binding affinity than parent JR11 (30-fold and 48-fold lower, respectively)
- Both showed high cell uptake but low internalization rate (consistent with antagonist behavior)
- SPECT/CT imaging showed high tumor accumulation for [177Lu]Lu-8a at 4, 24, 48, and 72 hours post-injection, comparable to JR11
- [177Lu]Lu-8b showed no tumor uptake despite in vitro activity
- Ex vivo biodistribution revealed increasing tumor uptake over time for 8a, but its extended blood circulation resulted in an unfavorable biodistribution profile for therapeutic use
Koustoulidou, Sofia; Handula, Maryana; de Ridder, Corrina; Stuurman, Debra; Beekman, Savanne; de Jong, Marion; Nonnekens, Julie; Seimbille, Yann ·
RPEP-06272 · 2022HNP1 bound to the SARS-CoV-2 Spike protein with submicromolar affinity — more than 20-fold stronger than its binding to serum albumin. Both HNP1 (an α-defensin) and retrocyclin RC-101 (a θ-defensin) interfered with Spike-mediated membrane fusion, Spike-pseudotyped lentivirus infection, and authentic SARS-CoV-2 infection in cell culture.
The mechanism involves defensins destabilizing and precipitating the Spike protein and inhibiting its interaction with the ACE2 receptor — the cellular entry point for SARS-CoV-2. This correlates with the known ability of defensins to unfold proteins with high conformational plasticity.
Serum reduced the antiviral activity of HNP1, likely due to competitive binding with serum proteins. However, at high concentrations, HNP1 still inactivated the virus even in serum, suggesting physiologically relevant antiviral potential.
Kudryashova, Elena; Zani, Ashley; Vilmen, Geraldine; Sharma, Amit; Lu, Wuyuan; Yount, Jacob S; Kudryashov, Dmitri S ·
RPEP-06276 · 2022Immunohistochemical analysis showed that normal thyroid tissue and benign thyroid disorders had virtually undetectable thymosin beta-4 (TMSB4X), with the exception of inflammatory cells in autoimmune thyroid disease. In contrast, TMSB4X was overexpressed across all thyroid cancer types examined: papillary, follicular, poorly differentiated, and undifferentiated.
Among 141 patients with differentiated thyroid cancer, higher TMSB4X expression was significantly associated with papillary tumor type, extrathyroidal extension (cancer growing beyond the thyroid gland), lymph node metastasis, and the presence of the BRAF V600E mutation. These findings were validated against public transcriptomic datasets.
Kuo, Chi-Yu; Jhuang, Jie-Yang; Huang, Wen-Chien; Cheng, Shih-Ping ·
RPEP-06277 · 2022The review identifies multiple neuropeptide systems implicated in anxiety and depression: oxytocin (anxiolytic and antidepressant properties), vasopressin (stress response regulation), neuropeptide Y (stress resilience and anti-anxiety effects), neuropeptide S (anxiolytic potential), and Substance P (pro-anxiety and pro-depressive when elevated, with NK1 antagonists showing antidepressant effects).
Many neuropeptides act as neuromodulators co-released with classical neurotransmitters, enabling communication between brain and body. The review notes that novel neuropeptides are increasingly being identified as having implications for mood disorder research, expanding the pool of potential therapeutic targets beyond traditional neurotransmitter-based approaches.
Kupcova, Ida; Danisovic, Lubos; Grgac, Ivan; Harsanyi, Stefan ·
RPEP-06281 · 2022Four novel pentapeptides derived from the 269-273 fragment of nucleophosmin 1 protein were designed and characterized. Three of four peptides showed typical shear-thinning profiles (meaning they flow when pushed but re-gel when force is removed — ideal for injection-based delivery) and self-assembled into hierarchical nanostructured fibers.
Two of the four peptides were biocompatible when tested with MCF7 cells. The study revealed that the terminal groups critically modulate hydrogel properties: C-terminal amidation caused the fastest aggregation and highest content of structured intermediates during the gelling process. This demonstrates that simple modifications to peptide ends can fine-tune hydrogel behavior.
La Manna, Sara; Florio, Daniele; Panzetta, Valeria; Roviello, Valentina; Netti, Paolo Antonio; Di Natale, Concetta; Marasco, Daniela ·
RPEP-06296 · 2022Rybelsus (oral semaglutide) was approved by the FDA, EMA, and PMDA following the PIONEER clinical program of ten Phase 3 randomized trials. The tablet formulation demonstrated comparable efficacy to injectable semaglutide for blood glucose lowering and weight loss, and superior efficacy compared to competitor products.
The key enabling technology was Emisphere's Eligen platform, which uses the absorption enhancer SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) to facilitate transepithelial absorption of the peptide from the stomach. This represented over 30 years of research and development to overcome the fundamental barriers to oral peptide delivery: gastrointestinal degradation, poor membrane permeability, and variable pharmacokinetics.
Lewis, Andrew L; McEntee, Nicholas; Holland, Justin; Patel, Asma ·
RPEP-06310 · 2022All four endosomolytic peptides (Aurein 1.2, GALA, HA2, and L17E) enhanced endosomal disruption when fused to EGFR-targeted protein conjugates, increasing the half-life of internalized protein and reducing lysosomal degradation. However, only Aurein 1.2 and GALA maintained EGFR-targeting specificity, while HA2 and L17E compromised the ability to selectively target cancer cells. This demonstrates that the choice of endosomal escape peptide significantly affects both targeting capability and bioactivity of the delivery system.
Lieser, Rachel M; Li, Qirun; Chen, Wilfred; Sullivan, Millicent O ·
RPEP-06311 · 2022Self-assembling peptide hydrogels made from the octapeptide FEFKFEFK (F8) could be formulated at acidic (pH 4) or basic (pH 9) conditions using the same peptide sequence. Acidic hydrogels induced a catabolic (degenerative) response in nucleus pulposus cells — increased expression of MMP-3, ADAMTS-4 degradative enzymes, neurotrophic factors NGF and BDNF, and NF-κB phosphorylation. Graphene oxide-containing acidic hydrogels (GO-F8) showed a milder inflammatory response with the highest expression of desired NP matrix proteins (aggrecan and collagen II). All systems buffered within 30 minutes in cell culture media, and the cellular pH response was transitory, peaking at 3 days and decreasing by 7 days.
Ligorio, Cosimo; Vijayaraghavan, Aravind; Hoyland, Judith A; Saiani, Alberto ·
RPEP-06314 · 2022The review covers aggregation behavior across the major therapeutic peptide families used in metabolic disease:
- Insulin and insulin analogs — the original and most-studied therapeutic peptide, prone to amyloid fibril formation
- Amylin analogs (pramlintide, davalintide, cagrilintide) — based on a peptide that naturally forms amyloid in the pancreas
- GLP-1 receptor agonists (liraglutide, exenatide, semaglutide) — newer drugs with their own aggregation profiles
- Glucagon and related peptides
Improper formulation, storage, manipulation, and usage can lead to high molecular weight products (HMWP) that are either amorphous or amyloid in nature. These aggregates can cause loss of biological activity, short-term immune reactions, and long-term silent inactivation of the drug.
Lima, Luís Maurício T R; Icart, Luis Peña ·
RPEP-06316 · 2022Across three autism-related mouse models (16p11.2 deletion, Shank3 knockout, Fmr1 knockout), chronic intranasal oxytocin (0.6 IU daily for 28 days) did not produce significant changes in neuroanatomy as measured by structural MRI, though some trending effects were observed.
No significant effect on social behavior was found in any strain. The only significant behavioral finding was normalization of a grooming deficit in the Fmr1 knockout model. No other treatment effects survived multiple comparisons correction. The authors conclude that chronic oxytocin had limited effects, and no promising pattern of treatment susceptibility by genotype emerged.
Lindenmaier, Zsuzsa; Ellegood, Jacob; Stuive, Monique; Easson, Kaitlyn; Yee, Yohan; Fernandes, Darren; Foster, Jane; Anagnostou, Evdokia; Lerch, Jason P ·
RPEP-06322 · 2022Thymosin beta-4 alleviated ethanol-induced oxidative stress and apoptosis in human corneal keratocytes by upregulating protective factors (Bcl-2, catalase, CuZnSOD) and inhibiting the cell death marker Caspase-3. Tβ4 also promoted cell proliferation through upregulated Ki67 expression and accelerated corneal wound healing in both in vitro and in vivo models. In mouse corneas treated with ethanol, Tβ4 promoted reconstruction of the damaged corneal stroma, confirmed by fluorescein sodium staining and histological examination.
Liu, Jinghua; Guo, Chen; Hao, Peng; Wang, Peihong; Li, Linghan; Wang, Yuchuan; Li, Xuan ·
RPEP-06324 · 2022TP5 degradation followed pseudo-first-order kinetics and was primarily driven by luminal enzymes throughout the intestinal tract (duodenum, jejunum, ileum, and colon). Three enzyme inhibitors significantly reduced TP5 breakdown:
- Soybean trypsin and chymotrypsin inhibitors (SBTCI) — considerable decrease in peptidolysis
- Bestatin — significant reduction
- EDTA — significant reduction
Three lipid-based nanocarrier systems (microemulsions, niosomes, and solid lipid nanoparticles) loaded with TP5 and SBTCI provided superior protection against degradation by both luminal contents and mucosal homogenates for 6 hours, compared to the unprotected peptide in solution.
Liu, Mengyang; Svirskis, Darren; Proft, Thomas; Loh, Jacelyn; Chen, Shuo; Kang, Dali; Wen, Jingyuan ·
RPEP-06325 · 2022Researchers attached a peptide from the p53 tumor suppressor protein onto gold nanoparticles and were able to restore its natural helical shape — a shape it loses when floating freely in solution. This 'Goldbody' construct specifically bound to MDM2, the protein that normally disables p53 in cancer cells. Surface plasmon resonance confirmed strong, specific binding between the Goldbody and MDM2, demonstrating its potential as an MDM2 inhibitor that could reactivate the body's tumor suppression machinery.
Liu, Qi; Sheng, Lingjie; Liu, Yuan-Yuan; Gao, Tiange; Wang, Haifang; Liu, Yuanfang; Cao, Aoneng · In Vitro
RPEP-06328 · 2022The peptide-modified nanoparticles successfully delivered oxaliplatin to the cell nucleus and miR-320 to the cytoplasm in human tongue squamous carcinoma cells. The pH-responsive coating protected the peptides during blood circulation and exposed them at acidic tumor sites for active targeting.
This is the first study to demonstrate concurrent modulation of six major cancer signaling pathways (NRP1/Rac1, PI3K/Akt/mTOR, GSK-3β/FOXM1/β-catenin, P-gp/MRPs, KRAS/Erk/Oct4/Yap1, and N-cadherin/Vimentin/Slug), simultaneously inhibiting cancer growth, progression, and multidrug resistance. In mice bearing SAS tumors, the combination nanoparticles showed superior antitumor efficacy and remarkably decreased oxaliplatin-associated toxicities.
Lo, Yu-Li; Lin, Hua-Ching; Tseng, Wei-Hsuan ·
RPEP-06329 · 2022Crotalphine (100 µg/kg, oral) produced analgesia lasting up to 24 hours in a chronic neuropathic pain model (partial sciatic nerve ligation, 14 days post-surgery). The analgesic effect was mediated by both opioid receptors (mu, kappa, and delta — blocked by CTOP, nor-BNI, and naltrindole respectively) and cannabinoid receptors (CB1 and CB2 — blocked by AM251 and AM630).
Crotalphine also decreased spinal cord IL-6 release and shifted microglia from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, as demonstrated by reduced CD86 and increased CD206 expression in BV-2 cells in vitro.
Lopes, Flavia S R; Giardini, Aline C; Sant'Anna, Morena B; Kimura, Louise F; Bufalo, Michelle C; Vigerelli, Hugo; Zambelli, Vanessa O; Picolo, Gisele ·
RPEP-06331 · 2022Among 97 patients treated with CGRP monoclonal antibodies (33 galcanezumab, 13 fremanezumab, 51 erenumab), response rates for monthly headache day reduction were: 54.6% full responders (>50% reduction), 13.4% partial responders (30-50%), and 32% non-responders (<30%).
PID-5 personality assessment revealed that non-responders had significantly higher scores in disinhibition, particularly in anhedonia and depressivity facets. For painkiller use reduction, non-responders showed increased depressivity and distractibility. For disability (MIDAS) improvement, non-responders scored higher in antagonism and submissiveness. The pattern suggests that traits associated with depressed mood and difficulty experiencing pleasure predict poorer treatment response.
Lovati, Carlo; Bernasconi, Gianna; Capogrosso, Chiara; Molteni, Laura; Giorgetti, Federica; Dell'Osso, Bernardo; Pantoni, Leonardo ·
RPEP-06336 · 2022Eleven participants with Stage IIIC-IV colorectal cancer received weekly vaccinations with CEA and Her2/neu peptides combined with tetanus helper peptide and GM-CSF in Montanide ISA-51 adjuvant.
Safety: All participants experienced adverse events, with 82% being Grade 1-2 (mild to moderate) — most commonly fatigue and injection site reactions. Two participants (18%) had treatment-related dose-limiting Grade 3 events, both self-limiting.
Immunogenicity: Immune responses (T-cell responses to Her2 or CEA peptides) were detected in 70% of the 10 evaluable participants via interferon-gamma ELISpot assay.
Survival: Median overall survival was 16 months for the full cohort. Remarkably, among three patients enrolled with no evidence of disease, median overall survival was not reached after more than 10 years of follow-up.
Lynch, Kevin T; Squeo, Gabriella C; Kane, William J; Meneveau, Max O; Petroni, Gina; Olson, Walter C; Chianese-Bullock, Kimberly A; Slingluff, Craig L; Foley, Eugene F; Friel, Charles M ·
RPEP-06347 · 2022The Cell-based Approach Membrane Permeability Assay (CAMPA) successfully ranked the cell membrane permeability of 24 diverse peptides — including cell-penetrating peptides, stapled peptides, and macrocyclic peptides — using live THP-1 and AsPc-1 cells.
The method works by briefly exposing peptide-cell mixtures to deuterium oxide. Peptides outside cells undergo hydrogen-deuterium exchange and gain mass, while peptides inside cells are shielded from labeling. MALDI mass spectrometry detects the ratio of labeled to unlabeled peptides over time. Results correlated with previously published permeability data. The assay also distinguished between passive diffusion and active (endocytosis-mediated) transport when an endocytosis inhibitor was added.
Makarov, Alexey A; Jiang, Yuan; Sondey, Christopher; Zhang, Minjia; Mansueto, My Sam; Pirrone, Gregory F; Huang, Chunhui; Biswas, Kaustav; Duggal, Ruchia; Al-Sayah, Mohammad Ahmed; Regalado, Erik L; Mangion, Ian ·
RPEP-06350 · 2022Diabetic rats showed comprehensive spinal cord disruption:
- Behavioral: thermal hyperalgesia, mechanical allodynia, decreased locomotor activity
- Metabolic: increased glucose, insulin, HbA1c, HOMA-IR; decreased insulin sensitivity
- Inflammatory: increased IL-1β, NF-κB; decreased IL-10 and β-endorphin in spinal tissue
- Oxidative: increased MDA; decreased SOD activity
- Apoptotic: upregulated caspase-3 and Bax; downregulated Bcl-2
- Neurotrophic: downregulated NGF and GDNF
- Histological: structural changes, increased CD68+ microglia
Exenatide treatment (10 μg/kg SC twice daily for 2 weeks) restored most of these biomolecular, structural, and functional impairments, demonstrating comprehensive neuroprotection.
Mandour, Dalia A; Shalaby, Sally M; Bendary, M A ·
RPEP-06351 · 2022The review highlights two main delivery strategies compatible with synthetic proteins: cell-penetrating peptides (CPPs) and multiplexed bead loading (MBL). CPPs are short peptide sequences that can transport synthetic proteins across the cell membrane, while MBL uses physical methods to introduce proteins into cells.
These delivery methods enable the study of posttranslational modifications (PTMs) — chemical changes that happen to proteins after they are made — in living cells. This is significant because PTMs regulate critical cellular processes but cannot be precisely controlled through genetic manipulation alone. The authors demonstrate applications including tracking protein localization, degradation, folding, interactions, and involvement in liquid-liquid phase separation organelles.
Mann, Guy; Sadhu, Pradeep; Brik, Ashraf ·
RPEP-06352 · 2022Hybrid nanostructures combining carboxymethylcellulose (CMC), a pro-apoptotic KLA peptide, cell-penetrating cysteine, and fluorescent quantum dots (Ag-In-S) demonstrated superior performance against glioblastoma:
- In vitro: the peptide-bearing nanoconjugates showed higher killing activity against U-87 MG glioblastoma cells than doxorubicin (a standard chemotherapy drug)
- In vivo (CAM assay): the nanohybrids reduced glioblastoma tumor progression by 41% in area and showed antiangiogenic activity (inhibiting blood vessel formation that feeds tumors)
- The nanostructures formed stable vesicle-like carriers suitable for both passive and active tumor targeting
- Fluorescent properties enabled simultaneous bioimaging and intracellular tracking
Mansur, Alexandra A P; Paiva, Mayara R B; Cotta, Oliver A L; Silva, Luciana M; Carvalho, Isadora C; Capanema, Nádia S V; Carvalho, Sandhra M; Costa, Érica A; Martin, Nelson R; Ecco, Roselene; Santos, Beatriz S; Fialho, Silvia L; Lobato, Zélia I P; Mansur, Herman S ·
RPEP-06355 · 2022The researchers identified that LRPAP1 signal peptide-specific CD8 T cells were present in the blood of all tested healthy donors and patients with non-small cell lung adenocarcinoma, confirming the immune system's inherent capacity to target this antigen.
However, the natural peptide sequence was poorly presented by dendritic cells due to a weak-binding serine at the C-terminus. Replacing this serine with a valine dramatically improved HLA-A2 binding affinity and T cell stimulation. Critically, T cells primed with the valine-modified variant still recognized the natural serine version and responded to TAP-deficient cancer cells. A systematic screen of extended peptide variants identified a 24-mer N-terminally elongated synthetic long peptide as the optimal vaccine candidate, ready for clinical trial validation.
Marijt, Koen A; Griffioen, Lisa; Blijleven, Laura; van der Burg, Sjoerd H; van Hall, Thorbald ·
RPEP-06358 · 2022The biologically active core of the VDAC1 cholesterol transport-enhancing peptide was identified as the tetrapeptide RVTQ. From this core, synthetic oral derivatives were designed, with 11 showing activity and 4 demonstrating robust, specific androgen increases. The lead compound RdVTQ was profiled across the lifespan of Brown-Norway rats and increased testosterone levels. The mechanism works within the HPG axis, meaning the body's natural feedback system self-regulates the response — preventing testosterone from rising to supraphysiological (abuse-potential) levels. Both subcutaneous and oral administration routes were effective.
Martinez-Arguelles, Daniel B; Nedow, Jennifer W; Gukasyan, Hovhannes J; Papadopoulos, Vassilios ·
RPEP-06359 · 2022Gene therapy delivering thymosin beta-4 (TB4) — an actin-regulating peptide — prevented kidney damage in mice. When kidney-filtering cells (podocytes) were injured by the chemotherapy drug Adriamycin, TB4 levels in those cells dropped. Delivering TB4 via an adeno-associated viral vector increased circulating TB4 levels and prevented both podocyte loss and protein leakage into urine (albuminuria).
The protective mechanism was traced to TB4's ability to stabilize the actin cytoskeleton — the internal scaffolding that gives podocytes their unique shape. When Adriamycin disrupted this scaffolding in cell culture, adding TB4 restored its organization. The study also confirmed via single-cell RNA sequencing that injured podocytes specifically lose TB4 expression.
Mason, William J; Jafree, Daniyal J; Pomeranz, Gideon; Kolatsi-Joannou, Maria; Rottner, Antje K; Pacheco, Sabrina; Moulding, Dale A; Wolf, Anja; Kupatt, Christian; Peppiatt-Wildman, Claire; Papakrivopoulou, Eugenia; Riley, Paul R; Long, David A; Vasilopoulou, Elisavet · Animal Study
RPEP-06360 · 2022Kisspeptin plays a dual role in oocyte maturation. The well-known indirect pathway works through the brain: hypothalamic kisspeptin neurons stimulate GnRH release, which triggers FSH and LH secretion from the pituitary, driving follicle development and ovulation.
But this review highlights a newer finding: kisspeptin also acts directly on the oocyte itself. Kisspeptins are produced by granulosa cells in ovarian follicles, while kisspeptin receptors are expressed on the oocytes. In mice, loss of kisspeptin receptors in oocytes led to failure of oocyte maturation and ovulation, resembling premature ovarian insufficiency.
In vitro studies in rats, pigs, and sheep confirmed that kisspeptin directly stimulates oocyte maturation by triggering calcium release and activating ERK1/2 signaling. In human clinical trials, kisspeptin-54 has been successfully used to improve oocyte maturation in assisted reproductive technologies.
Masumi, Saeed; Lee, Eun Bee; Dilower, Iman; Upadhyaya, Sameer; Chakravarthi, V Praveen; Fields, Patrick E; Rumi, M A Karim · Review
RPEP-06363 · 2022The review identifies a specific orexin-serotonin axis running from the lateral hypothalamus to the dorsal raphe nucleus that co-regulates three key components of energy balance: food intake, spontaneous physical activity (SPA), and energy expenditure.
Orexin neurons in the lateral hypothalamus project to serotonin-producing neurons in the dorsal raphe nucleus, which then influence cortical and subcortical regions controlling movement, feeding, and calorie burning. The review also discusses how impaired serotonin function in animal obesity models, genetic variants in the serotonin system, and serotonin-targeting drugs (including SSRIs and uptake inhibitors) all affect obesity risk and treatment.
Mavanji, Vijayakumar; Pomonis, Brianna; Kotz, Catherine M ·
RPEP-06364 · 2022GLP-1 and GIP receptors in pancreatic beta cells share overlapping but distinct signaling pathways, both converging on cAMP to stimulate glucose-dependent insulin secretion. The review maps how tirzepatide — the first clinically successful dual GLP-1/GIP receptor agonist — exploits both pathways simultaneously.
A key mechanistic insight: tirzepatide acts as a biased agonist at the GLP-1 receptor (activating some signaling pathways more than others) while potently activating the GIP receptor. This combination of biased GLP-1R signaling plus full GIPR activation may explain tirzepatide's superior clinical performance over GLP-1-only drugs.
Mayendraraj, Ashok; Rosenkilde, Mette M; Gasbjerg, Lærke S · Review
RPEP-06365 · 2022In a randomized, double-blind, placebo-controlled crossover study of 37 men with autism and 37 controls, a single 24-IU dose of intranasal oxytocin did not significantly influence neural processes related to the anticipation of social or monetary rewards in either group.
Bayesian analyses provided moderate evidence favoring the null model over the alternative, suggesting the lack of effect is likely genuine rather than a power issue. Results were inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. Notably, there were no significant differences in reward-related brain function between autism and control groups under placebo either.
Mayer, Annalina V; Preckel, Katrin; Ihle, Kristin; Piecha, Fabian A; Junghanns, Klaus; Reiche, Stefan; Rademacher, Lena; Müller-Pinzler, Laura; Stolz, David S; Kamp-Becker, Inge; Stroth, Sanna; Roepke, Stefan; Küpper, Charlotte; Engert, Veronika; Singer, Tania; Kanske, Philipp; Paulus, Frieder M; Krach, Sören ·
RPEP-06367 · 2022Researchers identified four bed bug defensins (CL-defensin1, 2, 3a, and 3b) with highly conserved amino acid sequences, differing mainly in their signal and pro-peptide regions. When bed bugs were exposed to bacteria — either by injection or by feeding on blood containing bacteria — these defensins were upregulated in both the midgut and the rest of the body.
For the first time, the study demonstrated sex-specific and exposure-route-specific differences in defensin expression. Male and female bed bugs responded differently to the same bacterial challenge, and whether bacteria were injected or ingested produced distinct defensin activation patterns.
The responses also differed between Gram-positive (B. subtilis) and Gram-negative (E. coli) bacteria, showing the bed bug immune system can discriminate between bacterial types.
Meraj, Sanam; Dhari, Arshvir Singh; Mohr, Emerson; Lowenberger, Carl; Gries, Gerhard · Laboratory Study
RPEP-06368 · 2022Liraglutide — a GLP-1 receptor agonist primarily used for diabetes and weight loss — showed three distinct therapeutic effects against osteoarthritis in laboratory and animal experiments:
1. **Pain relief**: Intra-articular injection of liraglutide reduced pain-related behavior in a mouse OA model, likely through GLP-1R-mediated anti-inflammatory activity.
2. **Anti-inflammatory action**: Liraglutide dose-dependently decreased IL-6, PGE2, and nitric oxide secretion and inflammatory gene expression in cartilage cells and macrophages. It also shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.
3. **Cartilage protection**: Liraglutide significantly decreased the activity of metalloproteinases and aggrecanases — enzymes responsible for breaking down cartilage.
Meurot, C; Martin, C; Sudre, L; Breton, J; Bougault, C; Rattenbach, R; Bismuth, K; Jacques, C; Berenbaum, F · Animal Study
RPEP-06370 · 2022Kisspeptin administration significantly modulated sexual brain processing in women with HSDD — the first time this has been demonstrated in a clinical population. Specifically, kisspeptin deactivated the left inferior frontal gyrus (involved in behavioral inhibition) and activated the right postcentral and supramarginal gyrus during exposure to sexual stimuli.
Beyond brain imaging changes, kisspeptin produced measurable behavioral effects: women reported increased feelings of 'feeling sexy' compared to placebo. Increased activation of the posterior cingulate cortex with kisspeptin was associated with reduced sexual aversion — suggesting the peptide may help overcome the psychological barriers that characterize HSDD.
Mills, Edouard G; Sheridan, Rebecca; Byers, Alexander; Sherwood, Robin A; Alexander, Emma C; Bech, Paul; Wall, Matthew B; Mayneris-Perxachs, Jordi; Sherwood, Karolina; Sheridan, Alexander; Salem, Victoria; Owen, Benedict M; Clarke, Sophie A; Sheridan, Rupert; Sherwood, Robin; Dhillo, Waljit S · Randomized Double Blind Placebo Controlled Crossover Trial