RPEP-04327 · 2019Both pharmacological blockade of substance P's receptor (NK1R antagonist L-733,060) and genetic deletion of substance P provided significant neuroprotection after traumatic brain injury in mice. Both approaches reduced motor and memory deficits, lesion volume, brain swelling, and blood-brain barrier disruption. The protective mechanisms involved inhibition of mitochondrial cytochrome c release, caspase-3 activation (cell death), oxidative stress, and neuroinflammation. TBI increased substance P levels in serum and cortex and upregulated NK1R expression, with NK1R upregulation occurring independent of substance P levels.
Li, Qianqian; Wu, Xiao; Yang, Yanyan; Zhang, Yue; He, Fang; Xu, Xiang; Zhang, Ziwei; Tao, Luyang; Luo, Chengliang ·
RPEP-04328 · 2019The HPV16 E7 peptide (residues 44-62) was attached to the self-assembling peptide Q11 to create nanofibers used in two vaccination strategies:
Preventive: Nanofiber immunization almost completely suppressed TC-1 tumor growth and even prevented tumor re-establishment after a 6-week rest period
Therapeutic:
- 66.7% tumor-free rate in mice with 2-3 mm established tumors
- 50% tumor-free rate in mice with larger 5-6 mm tumors
- Significantly increased effector Th1 cells, cytotoxic T lymphocytes (CTLs), IFN-γ, and TNF-α
- Reduced Th2 cells, myeloid-derived suppressor cells (MDSCs), and IL-4 compared to controls
- Nanofibers outperformed unassembled peptides for treating larger established tumors
Li, Sijin; Zhang, Qishu; Bai, Hongmei; Huang, Weiwei; Shu, Congyan; Ye, Chao; Sun, Wenjia; Ma, Yanbing ·
RPEP-04337 · 2019A hybrid hydrogel combining the self-assembling peptide FEFKFEFK with graphene oxide (GO) nanoflakes achieved mechanical properties matching the nucleus pulposus (the gel-like core of spinal discs). The peptide coated GO flakes and formed short fibrils on their surface through strong molecular interactions. The GO-F820 hybrid hydrogel maintained high cell viability and metabolic activity of nucleus pulposus cells in 3D culture over 7 days. The hydrogel is injectable, making it suitable for minimally invasive delivery to degenerating discs.
Ligorio, Cosimo; Zhou, Mi; Wychowaniec, Jacek K; Zhu, Xinyi; Bartlam, Cian; Miller, Aline F; Vijayaraghavan, Aravind; Hoyland, Judith A; Saiani, Alberto ·
RPEP-04340 · 2019Peptides derived from the oncoprotein CD151 triggered active anti-tumor immunity in two mouse cancer models — H22 hepatoma (primary liver cancer) and 4T1 breast cancer lung metastases. The peptide vaccines activated CD8+IFNγ+ killer T cells and suppressed myeloid-derived suppressor cells (MDSCs), a key immunosuppressive population in tumors. Mice immunized with CD151 peptides showed prolonged survival in the lung metastasis model. CD151 was identified as an ideal tumor-associated antigen through proteomic analysis of radiation-stressed tumor cells.
Lin, Wanzun; Liu, Jun; Chen, Juhui; Li, Jiancheng; Qiu, Sufang; Ma, Jiayu; Lin, Xiandong; Zhang, Lurong; Wu, Junxin ·
RPEP-04341 · 2019In both humans and mice completely lacking neurokinin B:
- LH pulses were preserved but at reduced frequency (slow pulse rate)
- Opioid antagonism (blocking dynorphin with naloxone) increased LH pulse frequency
- Exogenous kisspeptin stimulated LH responses normally
- GnRH administration triggered normal pituitary responses
This demonstrates that:
1. Neither NKB nor dynorphin is required for GnRH pulse generation
2. Both peptides modulate pulse frequency in opposing directions (NKB accelerates, dynorphin decelerates)
3. Kisspeptin responsiveness is maintained regardless of NKB status
4. The fundamental pulse-generating mechanism exists independently of NKB/dynorphin signaling
Lippincott, Margaret F; León, Silvia; Chan, Yee-Ming; Fergani, Chrysanthi; Talbi, Rajae; Farooqi, I Sadaf; Jones, Christopher M; Arlt, Wiebke; Stewart, Susan E; Cole, Trevor R; Terasawa, Ei; Hall, Janet E; Shaw, Natalie D; Navarro, Victor M; Seminara, Stephanie Beth ·
RPEP-04347 · 2019A meta-analysis of 34 randomized controlled trials involving 50,452 patients with type 2 diabetes found no increased risk of cancer with GLP-1 receptor agonist use. The overall odds ratio was 1.04 (95% CI 0.94–1.15, p=0.46), meaning cancer rates were essentially the same between GLP-1 users and controls.
Breaking it down by drug: liraglutide (OR 1.08, p=0.38), exenatide (OR 1.00, p=1.00), semaglutide (OR 0.89, p=0.80), and albiglutide (OR 1.07, p=0.93) all showed no increased risk. A subanalysis of trials lasting more than 3 years also found no signal (OR 1.03, p=0.60).
Statistical heterogeneity was low across all comparisons, strengthening confidence in the finding.
Liu, Yufang; Zhang, Xiaomei; Chai, Sanbao; Zhao, Xin; Ji, Linong · Meta Analysis
RPEP-04349 · 2019Cg-BigDef1 from oyster showed salt-stable, broad-spectrum bactericidal activity including against multidrug-resistant clinical MRSA isolates. The ancestral N-terminal domain — lost during evolution toward vertebrate beta-defensins — was essential: the C-terminal beta-defensin-like domain alone was inactive. Upon bacterial contact, the N-terminal domain drove Cg-BigDef1 self-assembly into nanonets that entrapped and killed bacteria. This nanonet formation represents a previously unknown antimicrobial mechanism. The salt stability is attributed to the hydrophobic N-terminal domain enabling membrane interactions in high-salt environments where electrostatic interactions are impaired.
Loth, Karine; Vergnes, Agnès; Barreto, Cairé; Voisin, Sébastien N; Meudal, Hervé; Da Silva, Jennifer; Bressan, Albert; Belmadi, Nawal; Bachère, Evelyne; Aucagne, Vincent; Cazevielle, Chantal; Marchandin, Hélène; Rosa, Rafael Diego; Bulet, Philippe; Touqui, Lhousseine; Delmas, Agnès F; Destoumieux-Garzón, Delphine ·
RPEP-04351 · 2019Under normal conditions, natriuretic peptides (ANP and BNP) are synthesized in response to atrial cardiomyocyte stretch and increase natriuresis, diuresis, and vascular permeability through cGMP-mediated signaling at specific receptors.
In heart failure, despite enhanced cardiac natriuretic peptide secretion, their beneficial effects are diminished due to renal resistance to NP action. A 'BNP paradox' exists: the BNP forms measured by current clinical assays may not represent the physiologically active forms, meaning high BNP levels in blood tests don't necessarily indicate effective peptide function. Inhibiting cyclic nucleotide phosphodiesterases (which degrade cGMP) represents a therapeutic strategy to improve natriuretic peptide system efficiency, with recent data supporting improved quality of life and prognosis in heart failure patients.
Lugnier, Claire; Meyer, Alain; Charloux, Anne; Andrès, Emmanuel; Gény, Bernard; Talha, Samy ·
RPEP-04354 · 2019Multiple cancer vaccine platforms have been developed over three decades, ranging from live viral/bacterial agents to synthetic peptide vaccines. Peptide vaccines — using short protein fragments that mimic cancer antigens — can elicit tumor-specific cellular and humoral immune responses, and have shown tumor regression or shrinkage in select trials. Nanoparticle delivery systems for peptide vaccines are an active area of development to improve immune recognition.
However, cancer vaccines alone have achieved limited clinical success. The most promising approach is combining vaccines with other immunotherapies, particularly immune checkpoint inhibitors, to achieve reliable objective responses and survival benefit.
Maeng, Hoyoung M; Berzofsky, Jay A ·
RPEP-04360 · 2019Cyclic peptides can achieve oral bioavailability despite violating traditional drug-likeness rules (Lipinski's Rule of 5), but they must be carefully designed for intestinal permeability. The key design principles fall into three categories: physical property guidelines (controlling size, flexibility, and lipophilicity), macrocyclic ring strategies (optimizing the backbone structure), and side chain strategies (minimizing solvent-exposed polarity).
The overarching goal is to reduce the peptide's exposure of polar chemical groups to the surrounding environment while keeping other properties in favorable ranges. This balancing act allows peptide chemists to achieve gut absorption alongside other critical drug properties like solubility and ability to bind their target.
Mathiowetz, Alan M · Review
RPEP-04363 · 2019Mice that received the oral microparticle vaccine showed strong activation of IFN-γ+/CD8+ T cells (cancer-killing immune cells) when re-exposed to the SP17 antigen. Vaccinated animals had significantly less ascites and tumor volume compared to placebo-treated animals four weeks after tumor challenge (p = 0.005).
The microparticles were engineered with enteric coatings to survive the stomach, sustained-release polymers for prolonged antigen exposure, and Aleuria aurantia lectin to specifically target M cells in the gut's immune tissue — making this a sophisticated oral delivery platform for peptide-based cancer immunotherapy.
Mattila, Juha-Pekka; Mirandola, Leonardo; Chiriva-Internati, Maurizio ·
RPEP-04367 · 2019Activation of substance P-positive neurons in the dorsomedial habenula causes simultaneous release of glutamate, glycine, and substance P in the lateral interpeduncular nucleus (LIPN). These co-released signals have opposing effects on synaptic plasticity: glycine receptor activity inhibits long-lasting potentiation of glutamatergic synapses, while substance P enhances it.
Substance P achieves this potentiation through a specific cascade: it triggers endocannabinoid CB1 receptor-mediated suppression of GABAB receptor activity, which disinhibits the system and allows substance P to produce a long-lasting increase in glutamate release. Behaviorally, NK1R (the substance P receptor) in the IPN was specifically required for fear extinction but not for the initial fear conditioning, demonstrating a selective role in fear unlearning.
Melani, Riccardo; Von Itter, Richard; Jing, Deqiang; Koppensteiner, Peter; Ninan, Ipe ·
RPEP-04372 · 2019In the ACTIVE phase 3 trial, the peptide drug abaloparatide produced significantly higher bone mineral density (BMD) response rates than both placebo and teriparatide at all time points and thresholds measured.
At 18 months, 44.5% of abaloparatide patients achieved >3% BMD gains at all three skeletal sites (total hip, femoral neck, and lumbar spine) compared to just 32.0% for teriparatide and 1.9% for placebo. The superiority was evident as early as 6 months: 19.1% of abaloparatide patients were responders versus 6.5% for teriparatide and 0.9% for placebo. Results were consistent across the >0%, >3%, and >6% response thresholds.
Miller, P D; Hattersley, G; Lau, E; Fitzpatrick, L A; Harris, A G; Williams, G C; Hu, M-Y; Riis, B J; Russo, L; Christiansen, C · Randomized Controlled Trial
RPEP-04373 · 2019Both energy-dependent and energy-independent pathways were involved in the cellular uptake of Tat-conjugated polymeric micelles. At initial contact, Tat-conjugated micelles strongly accumulated on the cell surface before internalization.
Critically, increasing Tat coating density had two effects: it increased both the membrane-anchoring rate and the internalization rate, and it accelerated the energy-independent (direct translocation) pathway. This means higher Tat density doesn't just get more particles inside cells — it fundamentally changes how they enter, favoring the direct penetration route that bypasses endosomal trapping.
Ming, Yang; Xiao, Yao; Tian, Yuan; Zhou, Shaobing ·
RPEP-04375 · 2019The pipeline identified a KRAS G12V mutation-carrying spliced epitope that is produced by proteasomes, transported by TAP proteins, and efficiently presented on cell surfaces by HLA-A*02:01 complexes — the most prevalent HLA class I molecule.
This is significant because conventional (non-spliced) peptides from the KRAS G12V mutation have low affinity for predominant HLA types, limiting their use in immunotherapy to only a few patients. By leveraging the much larger diversity of proteasome-generated spliced peptides, this approach could enable T cell-based immunotherapies targeting KRAS mutations in large cohorts of cancer patients.
Mishto, Michele; Mansurkhodzhaev, Artem; Ying, Ge; Bitra, Aruna; Cordfunke, Robert A; Henze, Sarah; Paul, Debdas; Sidney, John; Urlaub, Henning; Neefjes, Jacques; Sette, Alessandro; Zajonc, Dirk M; Liepe, Juliane ·
RPEP-04376 · 2019The mother and fetus independently produce and metabolize natriuretic peptides (ANP and BNP) — their circulations do not share these peptide hormones. In 244 fetal samples (86 with congenital heart defects, 31 with arrhythmia, 127 controls), there was no correlation between maternal and fetal levels of either ANP or BNP.
A key difference emerged between the two peptides: fetal ANP exists exclusively in its mature form and is rapidly metabolized by the placenta and umbilical vessels (umbilical vein levels were roughly double arterial levels). Fetal BNP, however, circulates predominantly as precursor forms (proBNP, glycosylated variants), which may protect it from placental degradation — BNP levels were similar between umbilical vein and artery. This has important implications for using natriuretic peptides as biomarkers for fetal heart disease.
Miyoshi, Takekazu; Hosoda, Hiroshi; Miyazato, Mikiya; Kangawa, Kenji; Yoshimatsu, Jun; Minamino, Naoto · Clinical (Observational/Cross Sectional)
RPEP-04378 · 2019At 26 weeks, oral semaglutide 14 mg reduced HbA1c by 1.0 percentage point versus 0.2 for placebo (treatment difference: -0.8 percentage points; p<0.0001). Body weight decreased by 3.7 kg with semaglutide versus 1.1 kg with placebo (treatment difference: -2.7 kg; p<0.0001).
In the on-treatment analysis (excluding patients who discontinued or needed rescue medication), the HbA1c reduction was even larger: -1.1 versus -0.1 percentage points. Completion rates were 82% for semaglutide and 88% for placebo. More patients discontinued semaglutide due to adverse events (15% vs 5%), primarily gastrointestinal symptoms. Renal safety was consistent with the GLP-1 receptor agonist class.
Mosenzon, Ofri; Blicher, Thalia Marie; Rosenlund, Signe; Eriksson, Jan W; Heller, Simon; Hels, Ole Holm; Pratley, Richard; Sathyapalan, Thozhukat; Desouza, Cyrus · Randomized Controlled Trial
RPEP-04380 · 2019Diabetes significantly altered the expression of multiple antimicrobial peptide genes in the male reproductive tract:
- β-defensins (Defb1, 2, 21, 24, 27, 30) showed perturbed expression in the caput, cauda, and testis of diabetic rats
- Spag11 family antimicrobial proteins (Spag11a, c, t) were also disrupted
- Toll-like receptors (Tlr1-13) and NOD1/2 innate immune receptors showed altered expression patterns
- Insulin treatment could only modulate expression of some, not all, of these genes, suggesting permanent or insulin-independent damage to the innate immune defense system
Munipalli, Suresh Babu; Mounika, Marri Reddy; Aisha, Jamil; Yenugu, Suresh ·
RPEP-04391 · 2019Three first-in-class anti-CGRP monoclonal antibodies — erenumab, galcanezumab, and fremanezumab — have been approved for migraine prevention based on consistent phase 2 and phase 3 clinical trial data demonstrating both safety and efficacy for episodic and chronic migraine. These therapies offer advantages over conventional preventive treatments including rapid onset, sustained efficacy, a placebo-like safety profile, and no pharmacological interactions. However, the high cost of anti-CGRP mAbs makes careful patient selection essential to optimize treatment effectiveness and resource allocation.
Negro, Andrea; Martelletti, Paolo ·
RPEP-04393 · 2019P10, a novel peptide derived from LL-37, demonstrated dose-dependent killing of MRSA in multiple settings when formulated in hypromellose gel:
- Remained chemically stable and antibacterially active at 4°C for 16 months in hypromellose gel
- Reduced MRSA colonizing the stratum corneum (outer skin layer) on Leiden human epidermal models (LEMs)
- Eradicated MRSA biofilms on LEMs
- Dose-dependently reduced MRSA counts on ex-vivo human skin
- Showed no adverse effects on human skin models
Hypromellose gel outperformed Cetomacrogol cream and Softisan cream as a delivery vehicle. Notably, some cream bases (Cetomacrogol with Vaseline, Softisan) were toxic to the skin models themselves, while hypromellose gel was safe.
Nibbering, Peter H; Göblyös, Anikó; Adriaans, Alwin E; Cordfunke, Robert A; Ravensbergen, Bep; Rietveld, Marion H; Zwart, Sarah; Commandeur, Suzan; van Leeuwen, Remko; Haisma, Elisabeth M; Schimmel, Kirsten J M; den Hartigh, Jan; Drijfhout, Jan Wouter; Ghalbzouri, Abdoelwaheb El ·
RPEP-04394 · 2019In 174 chronic hemodialysis patients without acute coronary syndrome, troponin T (cTnT) correlated strongly with BNP (r=0.531, p<0.001) and ANP (r=0.411, p<0.001). However, elevated cTnT was not associated with the presence or extent of coronary artery disease (CAD), unlike BNP and ANP which were.
All three biomarkers correlated independently with left ventricular end-diastolic pressure (LVEDP) and were associated with NYHA heart failure classification and peripheral artery disease. For prognosis, both cTnT and BNP predicted mortality and heart failure hospitalization, but only BNP predicted vascular events. This indicates cTnT elevation in dialysis patients reflects myocardial stress (heart failure) rather than atherosclerotic disease.
Niizuma, Shinichiro; Iwanaga, Yoshitaka; Washio, Takehiko; Ashida, Tadashi; Harasawa, Shinsuke; Miyazaki, Shunichi; Matsumoto, Naoya ·
RPEP-04399 · 2019L-cells in the gastrointestinal epithelium secrete GLP-1 in response to luminal factors — including short-chain fatty acids, bile acids, and microbial metabolites — that are specifically altered in IBS patients. GLP-1 can act as a hormone, paracrine factor, or neuromodulator, interacting with the HPA stress axis, immune system, and gut neurons, all of which are dysregulated in IBS.
A GLP-1 mimetic has been found to alleviate acute pain symptoms in IBS patients, providing early clinical evidence that GLP-1 signaling may be important in IBS symptom manifestation. The review proposes that GLP-1 and L-cells function as signal transducers in the microbiome-gut-brain axis.
O'Malley, Dervla ·
RPEP-04401 · 2019BNP (brain natriuretic peptide) plays a protective role in both the heart and kidneys, functioning as a key mediator of the heart-kidney connection. The review reveals that BNP levels are elevated in chronic kidney disease patients even without heart disease — a finding whose mechanism had been unclear. Evidence suggests the kidney's renal medulla produces depressor substances, and extracts from kidney papillary tips can actually stimulate cardiomyocytes (heart muscle cells) to produce and secrete more BNP.
BNP appears to counteract the renin-angiotensin-aldosterone system (RAAS) — the hormonal system that raises blood pressure and promotes fluid retention — providing a natural protective mechanism against both heart failure and kidney disease progression.
Okamoto, Ryuji; Ali, Yusuf; Hashizume, Ryotaro; Suzuki, Noboru; Ito, Masaaki · Review
RPEP-04402 · 2019The newly designed cell-penetrating peptide Pas2r12, consisting of a tandem repeat penetration-accelerating sequence (FFLIG-FFLIG) fused to d-dodeca-arginine (r12), significantly enhanced both cellular uptake and cytosolic release of two test proteins: enhanced green fluorescent protein (EGFP) and immunoglobulin G (IgG, an antibody).
A key practical advantage is that Pas2r12 works by simple mixing with cargo proteins — no chemical cross-linking or conjugation is required to form delivery-competent complexes.
Mechanistic studies revealed the delivery process is energy-dependent, requires actin polymerization, and is specifically mediated by caveolae-mediated endocytosis. This was confirmed by inhibition with genistein and methyl-β-cyclodextrin (caveolae inhibitors) and siRNA knockdown of caveolin-1.
Okuda, Akiko; Tahara, Shinya; Hirose, Hisaaki; Takeuchi, Toshihide; Nakase, Ikuhiko; Ono, Atsushi; Takehashi, Masanori; Tanaka, Seigo; Futaki, Shiroh ·
RPEP-04406 · 2019The stapled peptides achieved multiple validated effects in human monocytic cells (THP-1): they were effectively internalized, reduced ASC speck formation (the visible sign of inflammasome assembly), suppressed caspase-1 processing, and inhibited both pro-IL-1β processing and the release of active IL-1β and IL-18 following NLRP3 inflammasome activation.
The peptides were designed using molecular modeling guided by molecular dynamics simulations to adopt α-helical conformations that specifically target the pyrin domain of ASC. By disrupting ASC filament formation — a crucial structural step in inflammasome assembly — the peptides blocked the entire downstream inflammatory cascade. This represents the first successful proof-of-concept for stapled peptides targeting ASC in the NLRP3 pathway.
Pal, Arumay; Neo, Kurt; Rajamani, Lakshminarayanan; Ferrer, Fernando Jose; Lane, David P; Verma, Chandra S; Mortellaro, Alessandra ·
RPEP-04408 · 2019Peptide-based vaccination therapy can induce tumor-specific immune responses by presenting antigen-derived peptides that help the immune system recognize and target cancer cells. This approach has emerged as a promising strategy particularly for colorectal cancer patients with advanced disease, where conventional treatments often fail due to drug resistance, toxicity, or incomplete tumor elimination.
The review highlights that personalized approaches — selecting peptides based on the clinicopathological and molecular features of individual tumors — may be more effective than one-size-fits-all vaccination strategies. When combined with conventional therapies, peptide vaccines could help eradicate residual micrometastases that lead to cancer recurrence.
Parizadeh, Seyed Mostafa; Jafarzadeh-Esfehani, Reza; Ghandehari, Maryam; Rezaei-Kalat, Afsaneh; Parizadeh, Seyed Mohammad Reza; Javanbakht, Afsane; Hassanian, Seyed Mahdi; Ferns, Gordon A; Khazaei, Majid; Avan, Amir ·
RPEP-04416 · 2019The Substance P/NK-1 receptor (SP/NK-1R) system is implicated in fibrotic processes across multiple organ systems, including wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, lung fibrosis, and liver fibrosis.
Recent studies have specifically demonstrated that Substance P plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of this fibrosis. The review proposes that NK-1R receptor antagonists could provide clinical solutions for treating fibrotic diseases more broadly.
Peng, Lei; Agogo, George O; Guo, Jianqiang; Yan, Ming ·
RPEP-04417 · 2019The UT receptor for urotensin II has unexpectedly complex biology that may explain failed clinical translation. Two endogenous ligands — UII and urotensin-related peptide (URP) — bind and activate the receptor differently. The receptor is not restricted to the plasma membrane but also exists intracellularly, potentially inducing different physiological responses. These properties could produce inconsistent but potent vasoactive effects, explaining why UT receptor antagonists showed promise in preclinical models of heart failure, pulmonary hypertension, atherosclerosis, and diabetes but failed to replicate these results in clinical studies.
Pereira-Castro, João; Brás-Silva, Carmen; Fontes-Sousa, Ana Patrícia ·
RPEP-04423 · 2019Both intracerebroventricular (ICV) and intra-arcuate nucleus (ARC) injection of ghrelin significantly reduced pain behavioral scores across all phases of the formalin test (p < 0.01). Simultaneously, concentrations of met-enkephalin (MENK) and beta-endorphin (β-EP) in the periaqueductal gray area increased significantly following ghrelin injection. This demonstrates that ghrelin's pain-relieving effect operates through the arcuate nucleus and involves activation of the endogenous opioid system.
Pirzadeh, Samaneh; Sajedianfard, Javad; Aloisi, Anna Maria; Ashrafi, Mahboobeh ·
RPEP-04424 · 2019The review identifies three major categories of mitochondrial peptides with therapeutic potential:
1. Mitochondrial-derived peptides (MDPs): Humanin, humanin-like peptides, and MOTS-c are encoded by mitochondrial DNA and serve as protective stress response factors. These peptides have shown cytoprotective and metabolic-regulating effects in preclinical studies.
2. β-amyloid accumulation: The abnormal deposition of β-amyloid peptide within the mitochondrial matrix contributes to mitochondrial dysfunction in neurodegenerative diseases, representing both a disease mechanism and a therapeutic target.
3. Mitochondrial-targeting peptides: Engineered cell-penetrating peptides that can deliver bioactive agents directly into dysfunctional mitochondria, offering a strategy to restore electron transport chain function and cellular energy production in disease states.
Popov, Lucia-Doina ·
RPEP-04426 · 2019Patients who received collagen peptides (TENDOFORTE®) for the first 3 months showed a VISA-A improvement of 12.6 points, compared to only 5.3 points in the placebo group over the same period. After crossover, the group switching to collagen peptides saw a dramatic 17.7-point increase, while the group switching to placebo showed only a 5.9-point increase. Tendon microvascularity decreased in both groups, moderately correlating with clinical improvement (Rc²=0.68). No adverse events were reported.
Praet, Stephan F E; Purdam, Craig R; Welvaert, Marijke; Vlahovich, Nicole; Lovell, Gregg; Burke, Louise M; Gaida, Jamie E; Manzanero, Silvia; Hughes, David; Waddington, Gordon ·
RPEP-04428 · 2019Host defense peptides (HDPs), including cathelicidins and defensins, play complex dual roles at inflammation sites — acting as both pro-inflammatory and anti-inflammatory mediators depending on their concentration and context. HDPs provide constitutive protection against microorganisms but are also induced by inflammatory signals in various cells and tissues. Their physicochemical properties and interactions with multiple receptors determine whether they amplify or dampen inflammation. Impaired HDP expression is clinically relevant in several inflammatory diseases.
Prasad, Suhanya V; Fiedoruk, Krzysztof; Daniluk, Tamara; Piktel, Ewelina; Bucki, Robert ·
RPEP-04433 · 2019All three Cu-64-labeled affibody variants demonstrated excellent HER2 targeting with similar tumor uptake at 24 hours (4.0-4.3 %ID/g). The binding affinities were in the low nanomolar range: [64Cu]DOTA-Cys-ZHER2:342 (KD = 25.2 ± 9.2 nM) showed the strongest binding, followed by the C-terminal variant (32.6 ± 14.7 nM) and the internal variant (77.6 ± 22.2 nM).
The N-terminal labeled probe ([64Cu]DOTA-Cys-ZHER2:342) also demonstrated the highest in vivo stability. Specificity was confirmed by co-injecting unlabeled affibody, which reduced tumor uptake. All probes showed fast tumor targeting, good tumor accumulation, and good tumor-to-normal tissue contrast on PET imaging.
Qi, Shibo; Hoppmann, Susan; Xu, Yingding; Cheng, Zhen ·
RPEP-04437 · 2019EGCG was successfully encapsulated in solid lipid nanoparticles (SLNs) and conjugated with bombesin, a peptide that targets gastrin-releasing peptide receptors (GRPR) overexpressed on breast cancer cells. In vitro, the bombesin-conjugated formulation showed greater cytotoxicity to cancer cell lines compared to non-conjugated nanoparticles.
In vivo experiments in C57/BL6 mice with breast tumors demonstrated that the peptide-conjugated formulation produced greater tumor volume reduction and improved survival compared to both non-conjugated nanoparticles and plain EGCG. The results demonstrate that peptide-mediated targeting significantly enhances the therapeutic efficacy of EGCG delivery for breast cancer.
Radhakrishnan, Rasika; Pooja, Deep; Kulhari, Hitesh; Gudem, Sagarika; Ravuri, Halley Gora; Bhargava, Suresh; Ramakrishna, Sistla ·
RPEP-04438 · 2019Combining a positively charged peptide amphiphile (PA) with the negatively charged synthetic polymer PSS created hybrid hydrogels through supramolecular self-assembly. These PSS/PA hydrogels exhibited high mechanical stiffness, stability in buffered environments, and a nanofibrous structure resembling natural extracellular matrix.
The hydrogels could retain and sustainably release proteins of different charges — useful for controlled growth factor delivery. The sulfonate groups in PSS promoted controllable mineralization in osteogenic conditions. Human mesenchymal stem cells encapsulated in the hydrogels remained viable, demonstrating biocompatibility and potential for stem cell-based tissue engineering.
Radvar, Elham; Azevedo, Helena S ·
RPEP-04442 · 2019The global regulatory landscape for peptide-based therapeutics (PbTs) suffers from a significant lack of harmonization. Different pharmacopoeias (the official standards books used by regulators in different countries) use different test methods, specifications, and quality standards for the same peptide drugs. This inconsistency creates barriers for the global pharmaceutical industry and could slow the adoption of new peptide therapeutics.
The review identifies peptides' core advantages — high selectivity, strong efficacy, and low toxicity — as driving increased industry investment. However, the authors argue that standardizing quality specifications and test methods across international pharmacopoeias would further accelerate peptide drug development and global market access.
Rastogi, Shruti; Shukla, Shatrunajay; Kalaivani, M; Singh, Gyanendra Nath · Review
RPEP-04446 · 2019Thymosin β4 (Tβ4), a naturally occurring peptide known for roles in wound healing and tissue repair, promoted a specialized form of autophagy (noncanonical autophagy) in both human and mouse cells from chronic granulomatous disease (CGD) — a genetic immune disorder. The peptide worked by stabilizing HIF-1α, a protein that was abnormally low in CGD cells, which in turn activated autophagy and genes that protect mucosal barriers. In CGD mice with either colitis or aspergillosis (a fungal infection), Tβ4 treatment reduced inflammation, decreased granuloma formation, and improved survival. The study establishes Tβ4 as a potential therapeutic for CGD through a specific, druggable pathway.
Renga, Giorgia; Oikonomou, Vasilis; Moretti, Silvia; Stincardini, Claudia; Bellet, Marina M; Pariano, Marilena; Bartoli, Andrea; Brancorsini, Stefano; Mosci, Paolo; Finocchi, Andrea; Rossi, Paolo; Costantini, Claudio; Garaci, Enrico; Goldstein, Allan L; Romani, Luigina · In Vitro + Animal Study
RPEP-04448 · 2019The neoantigen prediction workflow involves multiple computational steps: somatic mutation identification from tumor-normal sequencing, HLA typing to determine the patient's immune molecule profile, peptide processing prediction, and peptide-MHC binding prediction. The authors provide specific recommendations for each step and identify key areas needing improvement, including HLA class II typing accuracy, software support for diverse neoantigen sources beyond point mutations, and incorporation of clinical response data to improve prediction algorithms. Currently, there is no consensus approach, and the field needs standardization.
Richters, Megan M; Xia, Huiming; Campbell, Katie M; Gillanders, William E; Griffith, Obi L; Griffith, Malachi ·
RPEP-04450 · 2019In streptozotocin-induced type 1 diabetic rats, C-fiber nociceptors in the temporomandibular joint became hyporesponsive starting from day 7 after disease induction. This was associated with significantly reduced protein levels of the neuropeptides substance P and calcitonin gene-related peptide (CGRP).
Paradoxically, while pain sensing decreased, inflammatory markers increased — higher levels of pro-inflammatory cytokine IL-1β and chemokine CINC-1/CXCL-1 were observed. PKC-α/β inhibitor (GO6976) or PKC-β inhibitor (LY333531) treatment restored capsaicin-induced nociception and increased Na+/K+-ATPase pump levels in the trigeminal ganglia.
The overall picture suggests diabetes creates a condition where tissue-damaging inflammation proceeds without pain perception, potentially leading to undetected joint degeneration.
Rocha-Neto, Luiz M; Gamarra-Suárez, Jaime R; Freitas, Fabiana F; Muzilli, Augusto; Abdalla, Henrique B; Macedo, Cristina G; Napimoga, Marcelo H; Clemente-Napimoga, Juliana T ·
RPEP-04454 · 2019Arcuate kisspeptin neurons serve as the critical link between your body's energy status and its reproductive system. These neurons are now recognized as the "command neurons" that drive the pulsatile release of GnRH — the master reproductive hormone. Crucially, kisspeptin neurons express receptors for metabolic hormones like insulin and leptin, meaning they can directly sense the body's energy reserves.
This dual role explains a long-standing mystery: how does the brain know to shut down fertility when energy is scarce? GnRH neurons themselves lack receptors for most metabolic hormones, so they can't sense energy status directly. Kisspeptin neurons bridge this gap — they respond to insulin and leptin (similar to POMC neurons), and they have direct synaptic connections to both GnRH neurons and the POMC/NPY-AgRP appetite circuits, making them a central coordinator of reproduction and metabolism.
Rønnekleiv, Oline K; Qiu, Jian; Kelly, Martin J · Review
RPEP-04455 · 2019The European Headache Federation formally recommends all four anti-CGRP monoclonal antibodies for migraine prevention. For episodic migraine, eptinezumab, erenumab, fremanezumab, and galcanezumab are recommended based on low to high quality evidence. For chronic migraine, erenumab, fremanezumab, and galcanezumab are recommended based on medium to high quality evidence.
One antibody (erenumab) targets the CGRP receptor, while the other three (eptinezumab, fremanezumab, galcanezumab) target the CGRP peptide itself. The guideline notes that for many clinical questions — like which patients to prioritize, when to switch between drugs, or how long to treat — evidence was insufficient and recommendations relied on expert opinion.
Sacco, Simona; Bendtsen, Lars; Ashina, Messoud; Reuter, Uwe; Terwindt, Gisela; Mitsikostas, Dimos-Dimitrios; Martelletti, Paolo · Guideline
RPEP-04457 · 2019The pH modifier excipient had the greatest impact on counterion loss during lyophilization of CSP7 peptide formulations. Optimizing the molar ratio of bulking agent to CSP7 preserved volatile compounds after lyophilization.
Higher chamber pressure during lyophilization lowered the sublimation rate of volatile compounds, helping retain counterions. Loss of volatile counterions caused pH shifts in reconstituted solutions, which in turn triggered peptide aggregation and reduced stability. Different salt forms of CSP7 (acetate vs. trifluoroacetate counterions) affected counterion volatilization differently. The study demonstrates that both formulation composition and processing parameters must be optimized together to maintain peptide drug stability.
Sahakijpijarn, Sawittree; Moon, Chaeho; Koleng, John J; Williams, Robert O ·
RPEP-04460 · 2019A. madurae achieved intracellular replication in HaCaT keratinocytes early in infection, but the cells eventually controlled the bacterial growth. In response to infection, keratinocytes overexpressed Toll-like receptors TLR2 and TLR6, and produced high concentrations of the antimicrobial peptides LL-37, human beta-defensin-1 (hBD-1), and human beta-defensin-2 (hBD-2).
The infected cells also released inflammatory chemokines and cytokines including monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), which recruit immune cells to the infection site. Tumor necrosis factor alpha (TNFα) was produced at lower levels. These findings demonstrate that keratinocytes are active participants in the immune defense against actinomycetoma, not just passive barriers.
Santiago-Téllez, Alfonso; Castrillón-Rivera, Laura Estela; Palma-Ramos, Alejandro; Bello-López, Juan Manuel; Sainz-Espuñes, Teresita; Contreras-Paredes, Adriana; Luna-Herrera, Julieta; Castañeda-Sánchez, Jorge Ismael ·
RPEP-04463 · 2019GHRH agonists of the JI and MR class demonstrated broad therapeutic potential across multiple organ systems in preclinical studies. MR-409 improved pancreatic β-cell proliferation and metabolic function, and facilitated islet engraftment after transplantation in rodents, offering a new approach to diabetes treatment.
In cardiac models, GHRH agonists improved ejection fraction and reduced infarct size in rats, reduced infarct scar in swine, and attenuated cardiac hypertrophy in mice. Notably, while GHRH agonists stimulated cancer cell growth in vitro, they inhibited tumor growth in vivo in xenograft models and downregulated GHRH receptors, suggesting a complex but potentially beneficial relationship with cancer biology.
Schally, Andrew V; Zhang, Xianyang; Cai, Renzhi; Hare, Joshua M; Granata, Riccarda; Bartoli, Manuela ·
RPEP-04464 · 2019Three cathelicidin antimicrobial peptides from different species — pig (PMAP-36), human (LL-37), and chicken (CATH-2) — kill E. coli bacteria through fundamentally different mechanisms despite being structurally similar peptides. Transmission electron microscopy revealed distinct killing patterns for each peptide.
Surprisingly, LL-37 binds bacterial endotoxin (LPS) very weakly compared to PMAP-36, yet it was the most potent at blocking LPS activation of immune cells (macrophages). This means strong LPS binding doesn't necessarily predict strong immunomodulatory activity.
Structure-activity analysis of PMAP-36 revealed that the first 11 amino acids at the N-terminal end could be removed without affecting bacterial killing, LPS neutralization, or binding. Cutting 4 more amino acids, however, dramatically reduced all activities. Shorter PMAP-36 analogs required dimerization (pairing up) for immunomodulatory function but not for bacterial killing — indicating these are separable activities.
Scheenstra, Maaike R; van den Belt, Matthias; Tjeerdsma-van Bokhoven, Johanna L M; Schneider, Viktoria A F; Ordonez, Soledad R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P · In Vitro Study
RPEP-04470 · 2019BPC 157 reversed liver fibrosis and portal hypertension in rats with surgically ligated bile ducts — a well-established model of chronic liver disease. Treatment with BPC 157 (at both 10 μg/kg and 10 ng/kg doses) through multiple routes (drinking water, intraperitoneal injection, or local application) reduced jaundice, ascites, liver nodularity, bile duct dilation, and liver weight abnormalities. At the cellular level, BPC 157 counteracted necrosis, apoptosis, inflammation, hepatic stellate cell activation (the cells that drive fibrosis), and collagen deposition.
Liver function markers normalized (AST, ALT, GGT, ALP, bilirubin improved; albumin increased). Tissue oxidative stress markers (MDA) and nitric oxide levels returned to healthy ranges, with changes in NOS2 and NOS3 expression and reduced inflammatory cytokines (IL-6, TNF-α, IL-1β). Portal hypertension was either prevented entirely or rapidly reversed depending on when BPC 157 treatment began.
Sever, Anita Zenko; Sever, Marko; Vidovic, Tinka; Lojo, Nermin; Kolenc, Danijela; Vuletic, Lovorka Batelja; Drmic, Domagoj; Kokot, Antonio; Zoricic, Ivan; Coric, Marijana; Vlainic, Josipa; Poljak, Ljiljana; Seiwerth, Sven; Sikiric, Predrag · Animal
RPEP-04474 · 2019Researchers created a chimeric vaccine platform by modifying the invariant chain (Ii) — a protein that helps present antigens to the immune system — and replacing its CLIP peptide region with melanoma antigen peptide sequences. When dendritic cells loaded with this modified construct were combined with a separate MHC-I vaccine platform and injected into tumor-bearing mice, the combination activated both CD4+ helper T cells and CD8+ killer T cells, inhibited melanoma tumor growth, and improved survival. The combination approach produced efficient tumor cell killing plus elevated Th1 and Th2 immune responses.
Sharbi-Yunger, Adi; Grees, Mareike; Cafri, Gal; Bassan, David; Eichmüller, Stefan B; Tzehoval, Esther; Utikal, Jochen; Umansky, Viktor; Eisenbach, Lea ·
RPEP-04483 · 2019Eye drops containing LyeTxI-b — a synthetic antimicrobial peptide designed from a Brazilian wolf spider (Lycosa erithrognatha) venom toxin — effectively treated resistant bacterial keratitis in rabbits with no signs of ocular toxicity. The peptide killed planktonic Staphylococcus aureus bacteria at a very low concentration (MIC 3.6 μmol/L), reduced biofilm viability by 90%, and when applied as drops four times daily for one week, eliminated bacteria and reduced inflammatory cell activity to levels comparable to healthy untreated eyes. Toxicity testing on chorioallantoic membranes and the standard Draize eye irritation test showed no adverse effects.
Silva, Carolina Nunes da; Silva, Flavia Rodrigues da; Dourado, Lays Fernanda Nunes; Reis, Pablo Victor Mendes Dos; Silva, Rummenigge Oliveira; Costa, Bruna Lopes da; Nunes, Paula Santos; Amaral, Flávio Almeida; Santos, Vera Lúcia Dos; de Lima, Maria Elena; Silva Cunha Júnior, Armando da · Animal Study
RPEP-04493 · 2019In a systematic comparison of resistance evolution against 14 antimicrobial peptides and 12 conventional antibiotics in E. coli, certain AMPs — specifically tachyplesin II and cecropin P1 — showed remarkably limited resistance development. Three lines of evidence supported this: (1) point mutations and gene amplification provided very low resistance levels against these AMPs, (2) bacteria already resistant to conventional antibiotics showed no cross-resistance to these AMPs, and (3) even when genomic fragments from a wide range of soil bacteria were introduced on plasmids, no detectable resistance to these AMPs emerged.
The researchers identified simple physicochemical features of AMPs that predict whether bacteria can evolve resistance — providing a roadmap for designing resistance-proof peptide antibiotics.
Spohn, Réka; Daruka, Lejla; Lázár, Viktória; Martins, Ana; Vidovics, Fanni; Grézal, Gábor; Méhi, Orsolya; Kintses, Bálint; Számel, Mónika; Jangir, Pramod K; Csörgő, Bálint; Györkei, Ádám; Bódi, Zoltán; Faragó, Anikó; Bodai, László; Földesi, Imre; Kata, Diána; Maróti, Gergely; Pap, Bernadett; Wirth, Roland; Papp, Balázs; Pál, Csaba · Basic Research
RPEP-04494 · 2019Peptain-1, a peptide with chaperone and anti-apoptotic properties, protected retinal ganglion cells (RGCs) from death in two rodent models of glaucoma. When injected into the abdomen, the peptide crossed the blood-retinal barrier and reached the retina.
Key results across models:
- In ischemia/reperfusion injury mice: peptain-1 inhibited RGC loss and improved impaired axonal transport
- In rats with 5 weeks of elevated eye pressure: peptain-1 significantly reduced both RGC death and axon loss, and partially restored mitochondrial COX 6b2 levels
- In cell culture and retinal explants: peptain-1 significantly reduced hypoxia-induced RGC death compared to scrambled peptide control
Stankowska, Dorota L; Nam, Mi-Hyun; Nahomi, Rooban B; Chaphalkar, Renuka M; Nandi, Sandip K; Fudala, Rafal; Krishnamoorthy, Raghu R; Nagaraj, Ram H · Animal Study