RPEP-07046 · 2023Researchers designed eight peptides — four linear and four cyclic — built from repeating tryptophan-tryptophan-arginine-arginine (WWRR) units and tested them as molecular delivery vehicles. The cyclic peptide [WWRR]5 (called C4) was the clear winner, showing the highest cellular uptake of three different cargo molecules including a phosphopeptide, siRNA, and an antiviral drug (3TC).
None of the peptides showed significant toxicity to cells at 5 μM concentration. The uptake of C4 was concentration- and time-dependent, and entered cells through both energy-dependent (endocytosis) and energy-independent pathways, confirming it acts as a true cell-penetrating peptide.
Kim, Lois; Lohan, Sandeep; Moreno, Jonathan; Zoghebi, Khalid; Tiwari, Rakesh Kumar; Parang, Keykavous · In Vitro
RPEP-07047 · 2023Thymosin beta 4 (Tβ4) protected hippocampal neuronal cells (HT22) against the toxic effects of the prion protein fragment PrP (106-126). Tβ4 significantly reversed the drop in cell viability and the spike in reactive oxygen species (ROS) caused by PrP (106-126). It also reduced levels of apoptotic (cell death) proteins triggered by the prion fragment.
Importantly, Tβ4 maintained a competitive balance of neurotrophic factors — specifically nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) — along with their receptors (p75, TrkA, and TrkB). This suggests Tβ4 protects neurons by working through the neurotrophic factor signaling pathway rather than simply blocking the toxic peptide directly.
Kim, Sokho; Choi, Jihye; Kwon, Jungkee · In Vitro
RPEP-07050 · 2023Thymosin beta-4 (Tβ4) prevents fibrosis and scarring in multiple animal models by reducing inflammation, decreasing macrophage infiltration, lowering levels of pro-fibrotic mediators (TGFβ, IL-10, CTGF), and preventing fibroblast conversion to myofibroblasts. The result is normally aligned collagen fibers rather than disordered scar tissue.
The N-terminal fragment of Tβ4, a tetrapeptide called Ac-SDKP (acetyl-serine-aspartate-lysine-proline), carries the majority of anti-fibrotic activity. Remarkably, Ac-SDKP can not only prevent fibrosis but also reverse established fibrosis in animal models of liver, lung, heart, and kidney fibrosis.
Kleinman, Hynda K; Kulik, Veronika; Goldstein, Allan L ·
RPEP-07054 · 2023In propensity score-matched analysis of 205 pairs of diabetes patients, the proportion with gastric residue during esophagogastroduodenoscopy was significantly higher in GLP-1RA users: 5.4% versus 0.49% in non-users (p=0.004) — approximately an 11-fold increase.
The 11 GLP-1RA patients with gastric residue were taking various agents: liraglutide 1.8 mg daily (n=2), dulaglutide 0.75 mg weekly (n=5), semaglutide 0.5 mg weekly (n=2), and semaglutide 1.0 mg weekly (n=2). This suggests the effect is a class-wide phenomenon across different GLP-1RAs and dosing frequencies.
Kobori, Toshiko; Onishi, Yukiko; Yoshida, Yoko; Tahara, Tazu; Kikuchi, Takako; Kubota, Tetsuya; Iwamoto, Masahiko; Sawada, Tomonobu; Kobayashi, Reo; Fujiwara, Hiroaki; Kasuga, Masato ·
RPEP-07063 · 2023Eighty-eight patients with chronic migraine and medication overuse headache were divided into four groups: erenumab (19.3%), galcanezumab (29.6%), fremanezumab (25%), and conventional medications as control (26.1%). Ages ranged from 18 to 78 years (mean 44.1 ± 13.6), with 65 women and 23 men.
Over 6 months of follow-up, all three anti-CGRP monoclonal antibody groups showed a statistically significant reduction in headache days compared to the conventional treatment control group (P < 0.0001).
Krymchantowski, Abouch; Jevoux, Carla; Krymchantowski, Ana Gabriela; Silva-Néto, Raimundo Pereira ·
RPEP-07064 · 2023In a study of 172 patients with chronic migraine and medication overuse headache, the group receiving anti-CGRP monoclonal antibodies added to conventional treatment (n=114) had a significantly greater reduction in both headache days and symptomatic medication intake at 3 months compared to the control group on conventional treatment alone (n=58), with p<0.0001.
Both groups showed improvement — indicating that the medication withdrawal and preventive treatment protocol helped on its own — but the addition of anti-CGRP antibodies provided a statistically significant additional benefit.
Krymchantowski, Abouch V; Jevoux, Carla; Krymchantowski, Ana Gabriela; Silva-Néto, Raimundo Pereira ·
RPEP-07065 · 2023Bovine lactoferrin (LF) and its digestive peptides — including pepsin hydrolysate (LFH) and lactoferricin (LFcin) — significantly increased interferon-alpha (IFN-α) production from human immune cells when viral single-stranded RNA was present. Without viral RNA, lactoferrin had no effect on IFN-α levels, indicating it acts as an immune amplifier rather than a standalone activator.
Lactoferrin also upregulated expression of HLA-DR and CD86 on plasmacytoid dendritic cells (pDCs), markers of immune cell activation. The digestive peptide LFH and the antimicrobial fragment LFcin showed comparable activity, suggesting that lactoferrin retains its immune-boosting properties even after being broken down by stomach enzymes.
Kubo, Shutaro; Miyakawa, Momoko; Tada, Asuka; Oda, Hirotsugu; Motobayashi, Hideki; Iwabuchi, Sadahiro; Tamura, Shinobu; Tanaka, Miyuki; Hashimoto, Shinichi · In Vitro
RPEP-07070 · 2023At 10 g/day of collagen peptides over 6 months, significant improvements were seen in activities of daily living (p=0.031, effect size ηp²=0.096) and pain (p=0.037, ηp²=0.164), though pain improvements were limited to high-frequency exercisers (>180 min/week).
Mental component scores (VR-12 MCS) improved with 10 g/day over 3-9 months (p=0.017, ηp²=0.309). Physical component scores improved with 20 g/day over 3-9 months, but only in females (p=0.013, ηp²=0.582). The large effect sizes for mental health and female physical health outcomes are notable.
Kviatkovsky, Shiloah A; Hickner, Robert C; Cabre, Hannah E; Small, Stephanie D; Ormsbee, Michael J ·
RPEP-07075 · 2023Stapled (macrocyclic) analogues of the Pannexin1-blocking peptide 10Panx1 were developed with dramatically improved properties. Two analogues (SBL-PX1-42 and SBL-PX1-44) achieved 2-fold greater Panx1 channel inhibition compared to the native linear peptide and showed >30-fold longer half-lives in human plasma. A double-stapled variant (SBL-PX1-206) inhibited ATP release from endothelial cells and significantly reduced monocyte adhesion to inflamed endothelium, demonstrating potential for treating cardiovascular inflammatory disease.
Lamouroux, Arthur; Tournier, Malaury; Iaculli, Debora; Caufriez, Anne; Rusiecka, Olga M; Martin, Charlotte; Bes, Viviane; Carpio, Laureano E; Girardin, Yana; Loris, Remy; Tabernilla, Andrés; Molica, Filippo; Gozalbes, Rafael; Mayán, María D; Vinken, Mathieu; Kwak, Brenda R; Ballet, Steven ·
RPEP-07077 · 2023Collagen hydrolysates (CHs) — low molecular weight peptides (3–6 kDa) from industrially processed collagen — have shown positive results in clinical trials for osteoarthritis: decreased joint pain, increased mobility, and structural joint improvements. The biological activity comes from bioactive peptides released during digestion of the collagen hydrolysate.
However, the review identifies significant knowledge gaps: it's unclear how well these peptides survive digestion, how much actually reaches the joints (bioavailability), which specific peptide sequences are responsible for the benefits, and how different collagen hydrolysate products compare. Sources include bovine (most common), porcine, and fish (piscine) collagen, each potentially producing different bioactive peptide profiles.
Larder, Christina E; Iskandar, Michèle M; Kubow, Stan · Review
RPEP-07081 · 2023Among 236 dulaglutide users followed for one year, increasing age and higher estimated glomerular filtration rate (eGFR) significantly increased both adherence and treatment continuation. Baseline obesity and baseline use of sulfonylurea or insulin significantly reduced the likelihood of continuing dulaglutide.
Switching dulaglutide dose during treatment and baseline neuropathy were associated with higher proportion of days covered (PDC) and longer treatment duration. In patients at high cardiovascular risk, baseline hypertension and higher LDL-C levels increased the likelihood of adherence. Cardiovascular risk status itself did not significantly affect any adherence or persistence outcome.
Lee, David Seung U; Lee, Howard ·
RPEP-07083 · 2023AMP-BERT, a deep learning model based on the BERT transformer architecture, outperformed all other machine learning and deep learning methods at predicting whether a peptide sequence has antimicrobial activity. The model was fine-tuned to extract structural and functional features from peptide sequences and classify them as antimicrobial or non-antimicrobial. Using BERT's attention mechanism, the researchers also identified specific amino acid residues that contribute most to antimicrobial function, providing interpretable insights into what makes a peptide antimicrobial.
Lee, Hansol; Lee, Songyeon; Lee, Ingoo; Nam, Hojung ·
RPEP-07084 · 2023In NZBWF1 lupus mice compared to controls:
**Hippocampus**: Mild endothelial dysfunction markers (altered tPA, uPA, ICAM-1, VCAM-1, eNOS, KLF4) that worsened with age (2 vs. 7 months). VIP/PACAP system showed moderate changes.
**Striatum**: Robust endothelial activation markers even in young mice, with significant upregulation of the VIP/PACAP system including VIP, PACAP, and their receptors (PAC1, VPAC1, VPAC2). This suggests the striatum is more vulnerable to lupus-related vascular damage.
The key insight: the brain's endogenous neuropeptide defense system (VIP/PACAP) is activated in response to vascular damage but cannot effectively counteract the ongoing autoimmune injury.
Lee, Jayden; Thomas Broome, Sarah; Jansen, Margo Iris; Mandwie, Mawj; Logan, Grant J; Marzagalli, Rubina; Musumeci, Giuseppe; Castorina, Alessandro ·
RPEP-07086 · 2023High-quality evidence supports all four available anti-CGRP receptor monoclonal antibodies (erenumab, galcanezumab, fremanezumab, and eptinezumab) for migraine prevention in patients who have failed prior prophylactic therapies. Switching from one anti-CGRP antibody to another may benefit some non-responders. Evidence is currently insufficient to confirm or reject the efficacy of combining CGRP-targeting drugs with oral prophylactics or botulinum toxin A. Treatment termination strategies remain guided primarily by reimbursement policies rather than clinical evidence.
Lee, Mi Ji; Al-Karagholi, Mohammad Al-Mahdi; Reuter, Uwe ·
RPEP-07087 · 2023Daily oral intake of 1,650 mg of collagen peptide NS (CPNS) — rich in the bioactive dipeptides Gly-Pro and Pro-Hyp — produced statistically significant improvements in multiple skin health markers compared to placebo.
Skin desquamation (flaking) and hydration showed early improvements, reaching significance at 4 weeks. Skin wrinkling and elasticity required a longer treatment period, achieving significance at 12 weeks. The staggered timeline suggests collagen peptides may first address surface-level moisture and barrier function before influencing deeper structural properties like elasticity.
Lee, Miyeong; Kim, Eunjoung; Ahn, Hyunwoo; Son, Seokjun; Lee, Hyunjun ·
RPEP-07094 · 2023A topical eye serum containing multiple bioactive peptides significantly reduced wrinkles around the eyes after 28 days of daily use in 32 women aged 20-45. The study documented decreases in wrinkle number, depth, and volume in the crow's feet area, along with improvements in skin hydration, elasticity, and firmness that increased continuously throughout the study period. 75% of participants expressed overall satisfaction with their skin appearance after using the product, and no adverse reactions were reported.
Li, Fengzhu; Chen, Haowei; Chen, Dongxiao; Zhang, Bingjie; Shi, Qingying; He, Xihong; Zhao, Huabing; Wang, Fang · Clinical Trial
RPEP-07096 · 2023TAT-PHLPP9c, a 20-amino acid cell-penetrating peptide, administered intravenously during CPR after 12-minute asystolic arrest in mice significantly improved return of spontaneous circulation, mean arterial blood pressure, cerebral blood flow, cardiac and neurological function, and survival at both 4 hours and 5 days.
Mechanistically, the peptide works by inhibiting PHLPP1, enhancing AKT activation (but not PKC), decreasing pyruvate dehydrogenase phosphorylation and sorbitol production, and increasing ATP generation in heart and brain. It also reduced plasma taurine and glutamate — markers of cell damage. Critically, these protective benefits were validated in a swine model of ventricular fibrillation cardiac arrest, providing strong translational evidence.
Li, Jing; Zhu, Xiangdong; Oberdier, Matt T; Lee, Chunpei; Lin, Shaoxia; Fink, Sarah J; Justice, Cody N; Qin, Kevin; Begeman, Andrew W; Damen, Frederick C; Kim, Hajwa; Chen, Jiwang; Cai, Kejia; Halperin, Henry R; Vanden Hoek, Terry L ·
RPEP-07102 · 2023From 27 undecapeptides screened by molecular docking, GQEDYDRLRPL was identified as the best ACE inhibitor from S. rugosoannulata. Ten of its eleven amino acid residues interacted with the ACE receptor. The peptide bound ACE with strong affinity — kinetic binding constant of 9.26 × 10⁻⁷ M and thermodynamic binding constant of 3.06 × 10⁻⁶ M. Binding was exothermic and enthalpy-driven.
The peptide had an in vitro IC50 of 164.41 μmol/L for ACE inhibition. In vivo, oral gavage administration at low doses showed superior antihypertensive effects compared to controls. Molecular dynamics simulations revealed that the peptide caused significant structural fluctuations in ACE residues 340-355, which include two residues in the enzyme's active pocket.
Li, Wen; Chen, Wanchao; Wang, Jinbin; Li, Zhengpeng; Zhang, Zhong; Wu, Di; Yan, Mengqiu; Ma, Haile; Yang, Yan ·
RPEP-07106 · 2023Four protein fractions from Tartary buckwheat (albumin, globulin, prolamin, glutelin) were hydrolyzed with pepsin and trypsin. All showed ACE inhibitory activity, with albumin hydrolysate (AH) strongest:
- AH: 79.89% ACE inhibition at 0.2 mg/mL with the highest peptide yield (82.28%)
- Globulin hydrolysate: 71.84% inhibition
- Prolamin and glutelin hydrolysates: lower inhibition rates
After gel filtration and reversed-phase HPLC purification of the most active AH fraction, nano-LC-MS/MS identified 42 ACE inhibitory peptides. Of these, 14 were completely novel discoveries. Computational analysis confirmed potent ACE inhibitory potential for all 14 new peptides.
Li, Yongfu; Yang, Nan; Shi, Feng; Ye, Fei; Huang, Jinrong ·
RPEP-07107 · 2023The novel chol-CGYKK molecule was successfully synthesized by connecting the peptide CGYKK to cholesterol via a disulfide linker. When incorporated into cationic liposomes carrying spike protein mRNA, the system maintained approximately 90% encapsulation rate after six months at 4°C — addressing a critical stability limitation of current LNP-mRNA systems.
Among four formulations tested with different excipient ratios, formulated sample 1 showed the highest spike protein expression. Its transfection efficiency reached 66.7% compared to the commercial transfection reagent Lipofectamine 2000.
Safety evaluation showed no toxic effects from either the CGYKK peptide or the complete mRNA vaccine liposomes. In vivo studies demonstrated that the vaccine triggered an immune response, though it was not yet as strong as the LNP-based comparator group.
Li, Yuan; Ma, Wenlin; Su, Wen; Yan, Zhihong; Jia, Lin; Deng, Jie; Zhu, Ali; Xie, Yanbo; Li, Xinyi; Shao, Wanhui; Ma, Yuman; Che, Linze; Zhu, Tao; Wang, Haomeng; Li, Mingyuan; Yu, Peng ·
RPEP-07109 · 2023The peptide DIGGL was identified from Ulva prolifera protein hydrolysates with an IC50 value of 10.32 ± 0.96 μM for ACE inhibition, acting through a non-competitive mechanism primarily via three conventional hydrogen bonds with the enzyme.
In human umbilical vein endothelial cells, DIGGL activated endothelial nitric oxide synthase to increase NO production and reduced endothelin-1 secretion induced by angiotensin II. The peptide also promoted mouse splenocyte proliferation both alone and when co-incubated with immune stimulants (Con A or LPS), indicating immunomodulatory properties. Crucially, DIGGL remained active after simulated gastrointestinal digestion with pepsin and trypsin.
Li, Zhiyong; He, Yuan; He, Hongyan; Zhou, Weizhe; Li, Mengru; Lu, Aiming; Che, Tuanjie; Shen, Songdong ·
RPEP-07112 · 2023After a median follow-up of 62 months, nine of 22 patients were still alive. Six had no disease progression, two had castration-resistant disease on second-line therapy, and one had castration-refractory disease. Median time to PSA progression was 21 months, median overall survival was 62 months, and median prostate cancer-specific survival was 84 months.
Lack of immune response was an independent marker of prostate cancer death — patients who failed to mount an immune response to the vaccine had worse survival. Some patients showed unexpected late immune response surges without developing recurrence, suggesting ongoing immunological surveillance. These findings indicate clinical benefit of hTERT vaccination in a subgroup of patients.
Lilleby, Wolfgang; Seierstad, Therese; Inderberg, Else Marit; Hole, Knut Håkon ·
RPEP-07115 · 2023The researchers used computational modeling to design next-generation stapled peptide inhibitors targeting Bcr-Abl, the fusion protein that causes chronic myeloid leukemia (CML). By incorporating hydrocarbon staples — chemical cross-links that lock the peptide into a stable helical shape — they aimed to overcome the conformational instability and protease vulnerability of their previous 81-amino-acid inhibitor construct.
The team modeled both single and double staple configurations across full-length and truncated peptide versions, with and without a cell-penetrating peptide (CPP) component. They identified lead candidates predicted to maintain strong binding to Bcr-Abl's coiled-coil oligomerization domain while being more stable and resistant to degradation than the unstapled version. These candidates are proposed for experimental validation.
Lima, Maria Carolina P; Hornsby, Braxten D; Lim, Carol S; Cheatham, Thomas E · Computational
RPEP-07116 · 2023The systematic review identified 8 preclinical studies testing 11 different animal venom-derived antimicrobial peptides against MDR Acinetobacter baumannii. Most AMPs originated from arthropod venoms (scorpions, spiders), and all were positively charged and rich in lysine residues.
In vivo testing showed these peptides reduced MDR-Ab-induced lethality and bacterial load across three infection models: invasive (bacteremia and pneumonia) and superficial (wound infections). Critically, the venom-derived AMPs demonstrated pleiotropic effects beyond direct bacterial killing — including pro-healing, anti-inflammatory, and antioxidant activities — that contribute to infection treatment and tissue recovery.
Lima, William Gustavo; de Lima, Maria Elena ·
RPEP-07118 · 2023GLP-1 receptor agonist use in Australia grew 11-fold between 2014 and 2022, reaching approximately 120,000 users by July 2022. SGLT2 inhibitor growth was even more dramatic at 216-fold, reaching 250,000 users.
Critically, from 2022 onwards, about 1 in 5 new SGLT2i users didn't have type 2 diabetes — indicating expanding use for cardiovascular indications alone. Cardiologist-initiated prescriptions reached 10% of new SGLT2i starts by mid-2022. Among GLP-1 RA users with cardiovascular conditions, dulaglutide and semaglutide were the most commonly prescribed. Most new users of both drug classes had evidence of both diabetes and cardiovascular disease.
Lin, Jialing; Pearson, Sallie-Anne; Greenfield, Jerry R; Park, Kyeong Hye; Havard, Alys; Brieger, David; Day, Richard O; Falster, Michael O; de Oliveira Costa, Juliana · Observational
RPEP-07123 · 2023HBD-1 (human beta-defensin 1) mRNA expression was significantly decreased in the corpus mucosa of patients with type 2 diabetes compared to healthy controls. Both HBD-1 and HBD-3 were expressed in the stomach's corpus mucosa, with HBD-3 levels showing a negative correlation with vitamin D concentrations. Most participants had low vitamin D levels regardless of metabolic status.
Linn, Oliver; Menges, Bernhard; Lammert, Frank; Weber, Susanne N; Krawczyk, Marcin ·
RPEP-07130 · 2023PLGA-PEG nanoparticles were functionalized with T7 targeting peptide and R9 cell-penetrating peptide, yielding particles of 168-186 nm with high drug loading efficiency (>80%). In a transwell BBB model using bEnd.3 cells, the penetration efficiency ranked: T7/R9 dual-peptide NPs > T7-peptide NPs > peptide-free NPs > free palbociclib.
The dual-peptide modified nanoparticles enhanced U87-MG glioblastoma cell apoptosis by 2.3 to 6.5-fold relative to free palbociclib, with the dual-peptide formulation being the most effective. The sequential mechanism — BBB penetration facilitated by T7/R9, followed by targeting to glioma cells — demonstrated effective cytotoxicity and promoted cell death.
Lo, Yu-Chen; Lin, Wen-Jen ·
RPEP-07134 · 2023MR-409 activated the cAMP/PKA/CREB/IRS2 signaling axis in beta cells, inducing insulin receptor substrate 2 (IRS2) — a master regulator of beta cell survival and growth — in a PKA-dependent manner. This pathway activation was associated with decreased beta cell death and improved insulin secretion in both mouse and human islets exposed to pro-inflammatory cytokines.
In the streptozotocin-induced type 1 diabetes mouse model, MR-409-treated mice showed better glucose homeostasis, higher circulating insulin levels, and preservation of beta cell mass compared to untreated animals. Increased IRS2 expression was confirmed in vivo, providing mechanistic consistency with the in vitro findings.
Louzada, Ruy A; Blandino-Rosano, Manuel; Flores, Sebastian; Lubaczeuski, Camila; Cui, Tengjiao; Sha, Wei; Cai, Renzhi; Schally, Andrew V; Bernal-Mizrachi, Ernesto ·
RPEP-07135 · 2023A 68-year-old man with metastatic small bowel neuroendocrine tumor received his fourth cycle of 177Lu-DOTATATE PRRT only 48 hours after his last dose of octreotide LAR, compared to the approximately 4-week interval used for his first 3 cycles. Tumoral uptake was not reduced at all compared to previous cycles, suggesting octreotide LAR does not meaningfully compete with 177Lu-DOTATATE for somatostatin receptor binding in this timeframe.
Low, Han Chung; Tay, Young Soon; Ong, Simon Yew Kuang; Tham, Wei Ying; Yan, Sean Xuexian ·
RPEP-07139 · 2023Bobcat339 induced TET3 protein degradation specifically in hypothalamic AgRP neurons, leading to:
- **Increased neuropeptide expression**: Upregulation of AgRP (agouti-related peptide), NPY (neuropeptide Y), and VGAT (vesicular GABA transporter) — all drivers of feeding behavior.
- **Behavioral rescue in ABA model**: Increased food intake, decreased compulsive running wheel activity, and reduced lethality in the activity-based anorexia mouse model.
- **Conserved mechanism**: Bobcat339 stimulated AgRP, NPY, and VGAT expression in a TET3-dependent manner in both mouse and human neuronal cells, suggesting cross-species relevance.
- **Anxiolytic effects**: The treatment also reduced anxiety/depressive-like behaviors.
Lv, Haining; Catarino, Jonatas; Li, Da; Liu, Beibei; Gao, Xiao-Bing; Horvath, Tamas L; Huang, Yingqun ·
RPEP-07144 · 2023By computationally screening 160,000 possible four-amino-acid peptides against ACE (the enzyme targeted by blood pressure drugs like lisinopril), researchers identified the amino acid characteristics that make a peptide a strong ACE inhibitor. Tryptophan (Trp) was the most important amino acid, followed by tyrosine, phenylalanine, histidine, and arginine.
The top-performing tetrapeptides (WWNW, WRQF, WFRV, etc.) had IC50 values between 19.98 and 36.76 μM — potent for food-derived peptides. The binding was driven by salt bridges, π-π stacking, π-cation interactions, and hydrogen bonds. In a striking proof of concept, inserting eight tryptophan residues into rabbit skeletal muscle protein (which naturally has no tryptophan) gave it over 90% ACE inhibition, suggesting that tryptophan-rich meat proteins could have blood pressure benefits.
Ma, Mingzhe; Feng, Yinghui; Miao, Yulu; Shen, Qiang; Tang, Shuting; Dong, Juan; Zhang, John Z H; Zhang, Lujia · Computational
RPEP-07146 · 2023The specificity and cross-reactivity of substance P (SP) and neurokinin A (NKA) at NK1R and NK2R is determined by interactions between the amino acids preceding the shared FxGLM consensus motif and two receptor regions: the β-hairpin of extracellular loop 2 (ECL2) and a segment of the N-terminus leading into transmembrane helix 1. Positively charged residues R177 (NK1R) and K180 (NK2R) in ECL2 play vital roles in these interactions.
The N-terminal positions 1–3 of the peptide ligands were entirely dispensable for receptor activation, meaning the selectivity determinants reside in the central peptide region. Mutated and chimeric receptor constructs, along with modified ligands, cleanly swapped specificity between NK1R and NK2R as predicted by the structural model, validating the structure-activity hypotheses.
Madsen, Jesper J; Petersen, Jacob E; Christensen, Dan P; Hansen, Jakob B; Schwartz, Thue W; Frimurer, Thomas M; Olsen, Ole H ·
RPEP-07150 · 2023Ku-P4, derived from the intrinsically disordered tail extensions of Ku proteins, showed high cell internalization efficacy and biocompatibility. Biophysical studies identified the proline residue as crucial for maintaining the disordered state that enables both biocompatibility and cell penetration. Ku-P4 effectively condensed DNA into positively charged polyplexes that penetrated cell membranes and delivered plasmid DNA intracellularly. The peptides represent a new class of CPPs based on intrinsically disordered protein regions.
Maity, Biswanath; Moorthy, Hariharan; Govindaraju, Thimmaiah ·
RPEP-07151 · 2023The review compares three tiers of obesity treatment:
1. Lifestyle interventions and older pharmacotherapies: associated with less than 12% body weight reduction and no clear evidence of reduced major adverse cardiovascular events (MACE)
2. Bariatric surgery: achieves 20-30% body weight reduction and is associated with markedly lower subsequent MACE risk
3. Newer peptide-based pharmacotherapies (semaglutide, tirzepatide): show greater weight loss efficacy compared to older drugs and are being evaluated in cardiovascular outcomes trials
The review notes that obesity drug prescribing remains relatively rare, partly due to concerns about long-term safety, provider bias, and lack of clear MACE reduction evidence. However, if ongoing trials demonstrate cardiovascular benefits for the newer agents, this is likely to drive expanded use.
Maki, Kevin C; Kirkpatrick, Carol F; Allison, David B; Gadde, Kishore M ·
RPEP-07152 · 2023Seven classes of antimicrobial peptides have been identified from silkworms: attacins, cecropins, defensins, enbocins, gloverins, lebocins, and moricins. Each class has distinct structural features and antimicrobial mechanisms.
These peptides collectively exhibit activity against bacteria, fungi, and viruses. A key advantage noted is that microorganisms cannot easily develop resistance to AMPs due to their membrane-targeting mechanisms. The review describes the immune signaling pathways (including Toll and Imd pathways) that regulate AMP production in silkworms in response to pathogen invasion.
Makwana, Pooja; Rahul, Kamidi; Ito, Katsuhiko; Subhadra, Bindu ·
RPEP-07153 · 2023TcdB (toxin B) from C. difficile targets gut-innervating afferent neurons via Frizzled receptors (FZD1/2/7) and pericytes via CSPG4, stimulating secretion of substance P (SP) and CGRP from neurons and proinflammatory cytokines from pericytes. This drives neurogenic inflammation.
Key proof: selectively activating the TcdB enzymatic domain in sensory neurons alone was sufficient to cause major CDI-like colonic pathology. Conversely, mice lacking SP, CGRP, or the NK1R receptor showed reduced pathology. Blocking SP or CGRP signaling reduced both tissue damage and C. difficile bacterial burden in mice infected with standard and hypervirulent strains.
Manion, John; Musser, Melissa A; Kuziel, Gavin A; Liu, Min; Shepherd, Amy; Wang, Siyu; Lee, Pyung-Gang; Zhao, Leo; Zhang, Jie; Marreddy, Ravi K R; Goldsmith, Jeffrey D; Yuan, Ke; Hurdle, Julian G; Gerhard, Ralf; Jin, Rongsheng; Rakoff-Nahoum, Seth; Rao, Meenakshi; Dong, Min ·
RPEP-07155 · 2023The review identifies a key insight: current ACE inhibitors block both the C-domain and N-domain of ACE, which causes bradykinin to accumulate and trigger dry cough and angioedema. However, blood pressure regulation primarily involves the C-domain. Natural peptides — especially those with tryptophan at the C-terminal — could be designed or selected to inhibit only the C-domain, theoretically controlling blood pressure without the side effects.
The proposed discovery pipeline involves: isolating peptides from natural products, testing their stability against gastrointestinal enzymes (for oral delivery), selecting those with favorable amino acid compositions, and using molecular docking and dynamics to confirm C-domain-specific inhibition.
Manoharan, Sivananthan ·
RPEP-07156 · 2023Sustained neurohumoral activation involving the sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS), and arginine vasopressin system drives the progression of heart failure through tachycardia and increased vascular resistance.
Natriuretic peptides and catecholamines serve as biomarkers for these pathways and can help identify which patients will benefit from specific therapies. The introduction of sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor, or ARNI) represents a refinement in RAAS blockade by combining RAAS inhibition with enhanced natriuretic peptide activity through neprilysin blocking.
Manolis, Antonis A; Manolis, Theodora A; Manolis, Antonis S ·
RPEP-07157 · 2023A 57-year-old male with type 2 diabetes developed acute pancreatitis complicated by superior mesenteric vein thrombosis approximately four months after a dose increase of dulaglutide (a GLP-1 receptor agonist). The presentation was atypical — only mild abdominal pain without nausea or vomiting — despite imaging revealing an enlarged pancreatic head and mesenteric vein blood clot. Endoscopic ultrasound with biopsies confirmed acute pancreatitis. The patient was treated with heparin anticoagulation and supportive care, and the GLP-1 agonist was discontinued.
Manuel, Sebastian L; Lin, Frank; Kutty, Sinan M ·
RPEP-07160 · 2023This comprehensive review maps the current understanding of over two dozen endogenous opioid peptides — the body's natural painkillers and reward signals. Key insights include: the synthesis pathways for endomorphins (a class of opioid peptides) remain debated and only recently proposed; opioid peptide release varies dramatically by brain region, with peptides released from specific neural compartments rather than uniformly; the distance peptides diffuse from release sites and how long they last in brain tissue remain poorly understood.
As a translational case study, the review examines how naltrexone (NTX) — the FDA-approved medication for alcohol use disorder — works by blocking the effects of these endogenous peptides. Recent research has clarified which specific opioid peptide activities naltrexone prevents, advancing understanding of why this decades-old drug helps reduce alcohol craving and consumption.
Margolis, Elyssa B; Moulton, Madelyn G; Lambeth, Philip S; O'Meara, Matthew J · Review
RPEP-07164 · 2023This review examines the role of thymosin beta 4 (Tβ4) in glomerular disease — conditions affecting the kidney's filtration units that are a major driver of chronic kidney disease. Tβ4, which naturally sequesters G-actin (a building block of the cell's structural skeleton), has demonstrated potent anti-inflammatory effects in experimental models of injury across multiple organs including heart, kidney, liver, lung, and eye.
The review covers both endogenous Tβ4 (what the kidney naturally produces) and exogenous Tβ4 (administered as treatment), examining how each influences glomerular disease progression and the mechanisms behind these effects.
Mason, William J; Vasilopoulou, Elisavet · Review
RPEP-07165 · 2023Abaloparatide — a synthetic peptide analog of parathyroid hormone-related protein (PTHrP) — dose-dependently increased bone mineral density at all measured sites in postmenopausal Japanese women with osteoporosis over 48 weeks. The 80 µg dose produced striking results: 11.5% increase in lumbar spine BMD, 2.9% increase at total hip, and 2.4% at femoral neck. Even the lower 40 µg dose showed significant improvement (6.6% lumbar spine).
Bone formation markers (serum PINP) increased rapidly — by 67.3% and 140.7% at the 40 and 80 µg doses — indicating strong bone-building activity. Bone resorption markers (serum CTX) increased more slowly and modestly (16.4% and 34.5%), suggesting a favorable anabolic window where bone formation outpaces breakdown. Adverse events were mild to moderate and not dose-dependent.
Matsumoto, Toshio; Sone, Teruki; Yamashita, Akiko; Inoue, Tetsuo · Randomized Controlled Trial
RPEP-07166 · 2023Researchers discovered a previously unknown interaction between thymosin alpha 1 (Tα1), a thymic immune-modulating peptide, and galectin-1 (Gal-1), a protein involved in cancer progression, immune suppression, and blood vessel formation. Tα1 directly binds to Gal-1 and alters its biological activity in three key ways: it blocks Gal-1's ability to clump red blood cells (hemagglutination), inhibits the formation of new blood vessel structures by endothelial cells, and reduces cancer cell migration in wound healing assays.
Physico-chemical analysis revealed the molecular details of how Tα1 binds to Gal-1, identifying the specific interaction sites. This is the first study to demonstrate this protein-protein interaction, providing a concrete molecular mechanism that helps explain why Tα1 has such wide-ranging effects across different diseases.
Matteucci, Claudia; Nepravishta, Ridvan; Argaw-Denboba, Ayele; Mandaliti, Walter; Giovinazzo, Alessandro; Petrone, Vita; Balestrieri, Emanuela; Sinibaldi-Vallebona, Paola; Pica, Francesca; Paci, Maurizio; Garaci, Enrico · Basic Science (In Vitro)
RPEP-07173 · 2023Tirzepatide (GLP-1/GIP dual agonist) marks a new era where pharmacotherapy approaches bariatric surgery-level weight loss. Multiple gut hormone combination strategies are under investigation: GLP-1 + GIP (tirzepatide, already approved), GLP-1 + glucagon (for enhanced energy expenditure and fat metabolism), GLP-1 + GIP + glucagon triple agonists, and amylin analogs. Each additional hormone target complements GLP-1's appetite-suppressing effects through different mechanisms — GIP enhances insulin and may directly affect fat tissue, glucagon increases energy expenditure, and amylin slows gastric emptying and promotes satiety.
Melson, Eka; Miras, Alexander Dimitri; Papamargaritis, Dimitris ·
RPEP-07187 · 2023A man in his 70s developed an injection site rash on his lower abdomen after switching from dulaglutide (a GLP-1 RA) to tirzepatide (a dual GIP/GLP-1 RA). The rash resolved after stopping tirzepatide. Notably, the patient had tolerated dulaglutide without any injection site reactions, indicating a tirzepatide-specific skin reaction. This was reported as the first documented case of tirzepatide-induced injection site reaction.
Mizumoto, Junki ·
RPEP-07192 · 2023Salivary beta-defensin 2 levels were significantly lower in children with asthma after 4 weeks of inhaled corticosteroid therapy compared to pre-treatment levels. Salivary flow rate did not change significantly between the two time points, indicating the reduction in this antimicrobial peptide was not simply due to reduced saliva production but likely a direct effect of corticosteroid treatment on defensin expression.
Moosavi, M-S; Hosseinizade, P-S; Panahi, G; Shariat, M ·
RPEP-07196 · 2023CRB-913, a novel cannabinoid receptor 1 (CB1R) inverse agonist with 9.5-fold lower brain penetration than rimonabant, enhanced the weight loss effects of three GLP-1 peptide drugs in obese mice. Combinations produced body weight reductions of -32.6% with tirzepatide, -28.8% with semaglutide, and -16.8% with liraglutide by day 18. CRB-913 alone achieved -22% weight loss. Combinations also improved body fat content, liver triglycerides, and liver fat deposits. CRB-913's reduced brain penetration aims to avoid the psychiatric side effects that derailed the original CB1R blocker rimonabant.
Morningstar, Marshall; Kolodziej, Andrew; Ferreira, Suzie; Blumen, Tracy; Brake, Rachael; Cohen, Yuval ·
RPEP-07206 · 2023Water-soluble protein from the red alga Gracilariopsis chorda, when hydrolyzed by thermolysin, produced peptides with 92% ACE (angiotensin-converting enzyme) inhibitory activity, substantially outperforming its DPP-IV inhibitory and antioxidant (DPPH scavenging) activities. Two novel ACE-inhibitory peptides were identified: IDHY and LVVER. Molecular docking analysis showed IDHY to be a particularly promising ACE inhibitor. The source proteins — phycobiliproteins and RuBisCo — contain high proportions of hydrophobic (31.0–46.5%) and aromatic (5.1–46.5%) amino acid residues, favorable for ACE-inhibitory peptide generation. Most ACE-inhibitory peptide sequences were located in highly solvent-accessible α-helix regions of the parent proteins.
Mune Mune, Martin Alain; Miyabe, Yoshikatsu; Shimizu, Takeshi; Matsui, Wataru; Kumagai, Yuya; Kishimura, Hideki ·
RPEP-07212 · 2023The review presents evidence that p53 and AKT signaling pathways can have non-canonical (opposite to expected) functions in cancer: p53 can promote cell survival and AKT can promote cell death under certain conditions. The authors' own research found that Thymosin beta-4 (Tβ4) mediates chemosensitivity in medulloblastoma cells through an AKT-p53 interaction, suggesting the peptide could be leveraged to enhance drug sensitivity.
These context-dependent, interchangeable functions of p53 and AKT may be therapeutically exploitable, and Thymosin beta-4's role in modulating this interaction represents a potential new approach to treating medulloblastoma.
Naeem, Aisha; Knoer, Grace; Avantaggiati, Maria Laura; Rodriguez, Olga; Albanese, Chris ·
RPEP-07215 · 2023The study reveals a surprising mechanism by which allergic inflammation enables S. aureus colonization:
1. Th2 (allergic) inflammation via IL-4Rα activation reduces antimicrobial peptide production
2. This partial AMP reduction selectively kills coagulase-negative Staphylococcus (CoNS) strains that normally produce natural antibiotics against S. aureus
3. Without these protective bacteria, antibiotic-non-producing CoNS and S. aureus expand — recapitulating the microbiome seen in human atopic dermatitis
4. In Camp-/- mice or after topical steroids (which further suppress AMPs), paradoxically the antibiotic-producing CoNS survive because they're no longer selectively targeted
5. In Th17 inflammation, high AMP levels directly kill S. aureus — explaining why psoriasis patients (Th17-dominant) rarely get staph infections
This demonstrates a competitive dynamic where both host AMPs and bacterial-produced antibiotics cooperate to control S. aureus.
Nakatsuji, Teruaki; Brinton, Samantha L; Cavagnero, Kellen J; O'Neill, Alan M; Chen, Yang; Dokoshi, Tatsuya; Butcher, Anna M; Osuoji, Olive C; Shafiq, Faiza; Espinoza, Josh L; Dupont, Christopher L; Hata, Tissa R; Gallo, Richard L ·