Browse more peptide research, methods and limitations.
Human milk proteins (lactoferrin, lysozyme, sIgA, alpha-lactalbumin) and their digestion-generated bioactive peptides provide comprehensive antimicrobial, immunomodulatory, and trophic activities that protect and develop infant health.
Lönnerdal, Bo · Review
Maternal separation significantly altered maternal care patterns but produced only subtle changes in adult offspring brain opioid peptides and behavior, suggesting compensatory mechanisms partially buffer against early-life adversity effects.
Marmendal, Maarit; Roman, Erika; Eriksson, C J Peter; Nylander, Ingrid; Fahlke, Claudia · Animal Study
Ghrelin stimulated human adrenal zona glomerulosa cell proliferation via p42/p44 MAPK activation and simultaneously inhibited apoptosis through functional GHS-R — dual proliferogenic and anti-apoptotic adrenal effects.
Mazzocchi, Giuseppina; Neri, Giuliano; Rucinski, Marcin; Rebuffat, Piera; Spinazzi, Raffaella; Malendowicz, Ludwik K; Nussdorfer, Gastone G · In Vitro
Among equally obese adults (BMI ~32), those who were insulin-resistant had significantly lower ghrelin levels (252 pg/ml) than insulin-sensitive individuals (412 pg/ml; P<0.001) — a 39% difference. This finding separates the effect of insulin resistance from obesity itself on ghrelin suppression. Ghrelin correlated inversely with both insulin resistance (r = -0.64; P<0.001) and fasting insulin levels (r = -0.58; P<0.001). Multivariate analysis confirmed that both insulin resistance and high insulin levels independently predicted low ghrelin, suggesting that insulin resistance — not just being overweight — drives ghrelin suppression. This points to a metabolic feedback loop where insulin resistance further suppresses the hunger hormone, potentially disrupting normal appetite regulation.
McLaughlin, Tracey; Abbasi, Fahim; Lamendola, Cindy; Frayo, R Scott; Cummings, David E · Observational
CCK released by intestinal fat/protein is the primary short-term satiety signal, acting through vagal afferents and brain CCK-A receptors to reduce meal size — the best-characterized gut satiety peptide with therapeutic implications for obesity.
Moran, Timothy H; Kinzig, Kimberly P · Review
Both ghrelin forms inhibited isoproterenol-induced lipolysis in rat adipocytes, with the effect NOT mediated by GHS-R1a (des-acyl ghrelin was equally effective) — demonstrating fat metabolism regulation through an unidentified non-GHS-R receptor.
Muccioli, Giampiero; Pons, Nicoletta; Ghè, Corrado; Catapano, Filomena; Granata, Riccarda; Ghigo, Ezio · In Vitro
Opioid peptide conformations in membrane-mimetic environments differed significantly from solution structures, revealing the biologically relevant receptor-interacting conformations for structure-based opioid drug design.
Naito, Aira; Nishimura, Katsuyuki · Review
BNP plasma concentrations correlated significantly with infarct size measured by thallium-201 SPECT in MI patients, providing a blood test surrogate for imaging-determined infarction extent.
Nakagawa, Kazuya; Umetani, Ken; Fujioka, Daisuke; Sano, Keita; Nakamura, Takamitsu; Kodama, Yasushi; Kitta, Yoshinobu; Ichigi, Yoshihide; Kawabata, Ken-Ichi; Obata, Jyun-Ei; Takano, Hajime; Inobe, Yoshito; Kugiyama, Kiyotaka · Cross Sectional
Urinary N-BNP showed the best diagnostic performance for heart failure detection among urinary natriuretic peptides tested (N-ANP, N-BNP, CNP), offering a non-invasive urine-based alternative to blood sampling.
Ng, L L; Geeranavar, S; Jennings, S C; Loke, I; O'Brien, R J · Cross Sectional
N-terminal proANP predicted incident CHF in stable community heart disease patients, with elevated levels identifying those who would progress from compensated heart disease to symptomatic heart failure.
Nielsen, O W; Rasmussen, V; Christensen, N J; Hansen, J F · Cohort
Cardiac opioid peptide receptors (delta, kappa) and beta-adrenergic receptors share G-protein signaling pathways, creating functional cross-talk that modulates contractility, arrhythmia susceptibility, and ischemic preconditioning cardioprotection.
Pepe, Salvatore; van den Brink, Olivier W V; Lakatta, Edward G; Xiao, Rui-Ping · Review
Mice made obese through a high-fat diet developed resistance to ghrelin — the hunger hormone stopped working properly. Specifically, obese mice had lower circulating ghrelin levels, lost the normal daily rhythm of ghrelin secretion, and no longer showed the typical ghrelin spike during fasting and refeeding. When given exogenous ghrelin injections, obese mice ate significantly less in response compared to lean mice. Critically, when the obese mice lost weight, their sensitivity to ghrelin was restored. The authors suggest this means ghrelin inhibition after weight loss could potentially prevent weight regain — because ghrelin sensitivity returns precisely when it would drive overeating.
Perreault, M; Istrate, N; Wang, L; Nichols, A J; Tozzo, E; Stricker-Krongrad, A · Animal Study
PT-141 (melanocortin agonist) selectively increased sexual solicitation (proceptive) behavior in female rats without affecting locomotion or other behaviors — demonstrating specific melanocortin modulation of female sexual desire/motivation.
Pfaus, James G; Shadiack, Annette; Van Soest, Tanya; Tse, Maric; Molinoff, Perry · Animal Study
A 33-amino-acid gliadin peptide (the '33-mer'), naturally produced by gastrointestinal digestion of wheat gluten, is an exceptionally potent T cell stimulator in celiac disease. It contains six overlapping copies of three T cell epitopes and, after modification by tissue transglutaminase (TG2), binds with high affinity to the HLA-DQ2 immune molecule. Remarkably, the 33-mer doesn't need to be further processed inside immune cells — it can be presented to T cells directly, even by chemically fixed (non-living) antigen-presenting cells. It also binds DQ2 optimally at pH 6.3, promoting extracellular binding.
Qiao, Shuo-Wang; Bergseng, Elin; Molberg, Øyvind; Xia, Jiang; Fleckenstein, Burkhard; Khosla, Chaitan; Sollid, Ludvig M · In Vitro
Acetaminophen's spinal/supraspinal antinociceptive self-synergy was attenuated by opioid receptor antagonists in mice, demonstrating an opioid receptor component to acetaminophen's pain-relieving mechanism.
Raffa, Robert B; Walker, Ellen A; Sterious, Steven N · Animal Study
NT-proBNP serves as both a diagnostic tool and a treatment monitoring biomarker in heart failure, with serial measurements guiding drug titration and tracking therapeutic response for personalized care.
Richards, Mark; Troughton, Richard W · Review
SAR studies on astressin identified the minimal CRF antagonist sequence retaining biological activity at both CRF1 and CRF2 receptors, advancing design of smaller, more drug-like peptide antagonists for stress-related psychiatric disorders.
Rijkers, Dirk T S; Kruijtzer, John A W; van Oostenbrugge, Marja; Ronken, Eric; den Hartog, Jack A J; Liskamp, Rob M J · In Vitro
Thymosin alpha-1 activated dendritic cells for Th1 antifungal resistance through toll-like receptor (TLR) signaling pathways, providing a specific innate immune mechanism for its anti-infectious properties and positioning it for fungal infection immunotherapy.
Romani, Luigina; Bistoni, Francesco; Gaziano, Roberta; Bozza, Silvia; Montagnoli, Claudia; Perruccio, Katia; Pitzurra, Lucia; Bellocchio, Silvia; Velardi, Andrea; Rasi, Guido; Di Francesco, Paolo; Garaci, Enrico · In Vitro
Selective opioid receptor and peptide antibody blocking revealed delta-opioid (enkephalin) and kappa-opioid (dynorphin) systems as the primary contributors to myocardial ischemic tolerance, with quantified relative contributions of each endogenous opioid family.
Romano, Matthew A; Seymour, Elisabeth M; Berry, Jennifer A; McNish, Robert A; Bolling, Steven F · Animal Study
SC PT-141 induced dose-dependent erectile responses in ED patients (double-blind, placebo-controlled) with characterized pharmacokinetics, acceptable safety, and practical SC delivery — advancing toward clinical approval.
Rosen, R C; Diamond, L E; Earle, D C; Shadiack, A M; Molinoff, P B · RCT
Amygdalar NPY-CRF interactions constitute an anxiety-resilience balance: CRF promotes fear/anxiety through CRF1 while NPY opposes through Y1 receptors — imbalance drives anxiety disorders, PTSD, and addiction.
Sajdyk, Tammy J; Shekhar, Anantha; Gehlert, Donald R · Review
Lactoferrin-derived peptides showed anti-complement activity, inhibiting complement cascade activation and adding immune modulation beyond antimicrobial effects to the lactoferricin functional profile.
Samuelsen, Ørjan; Haukland, Hanne H; Ulvatne, Hilde; Vorland, Lars H · In Vitro
Gut peptide-based obesity drugs including GLP-1 agonists, PYY analogs, oxyntomodulin, and ghrelin antagonists represent the most promising peripheral anti-obesity targets, with GLP-1 showing the most advanced clinical development.
Scharf, Matthew T; Ahima, Rexford S · Review
Eating behavior in obesity reflects disrupted multi-level peptide signaling: blunted gut satiety peptides (GLP-1, PYY, CCK), altered opioid reward processing, ghrelin dysregulation, and impaired central neuropeptide circuits — biology driving behavioral excess.
Schwartz, Gary J · Review
Thymosin alpha-1 reprogrammed tumor-associated macrophages from immunosuppressive to tumoricidal phenotype, enabling them to kill cancer cells directly — overcoming a key immune evasion mechanism of the tumor microenvironment.
Shrivastava, P; Singh, S M; Singh, N · Animal Study
Thymosin alpha-1 promoted differentiation of tumor-associated macrophages into functional dendritic cells with enhanced antigen presentation and antitumor activity — converting tumor immune suppressor cells into effective cancer fighters.
Shrivastava, Pratima; Singh, Sukh Mahendra; Singh, Nisha · Animal Study
Peripheral gut hormone-based obesity drug development focuses on GLP-1 agonists (most advanced), PYY analogs, oxyntomodulin, amylin analogs, and PP as practical anti-obesity drug targets with established physiological rationale and clinical precedent.
Small, Caroline J; Bloom, Stephen R · Review
N-ANP and NT-proBNP both independently predicted cardiovascular events in stable community heart disease patients, with combined measurement providing superior risk stratification for identifying those who would develop CHF or cardiac death.
Squire, Iain B; O'Brien, Russell J; Demme, Bettina; Davies, Joan E; Ng, Leong L · Cohort
A mid-regional pro-adrenomedullin (MR-proADM) fragment was identified and quantified in sepsis patient plasma, providing a stable, measurable surrogate for the unstable mature adrenomedullin — establishing the basis for clinical MR-proADM sepsis testing.
Struck, Joachim; Tao, Chen; Morgenthaler, Nils G; Bergmann, Andreas · Clinical Trial
GHS-R knockout mice showed no GH release or appetite stimulation from ghrelin administration, definitively proving both effects require the GHS-R — settling the debate about whether ghrelin uses alternative receptors for appetite.
Sun, Yuxiang; Wang, Pei; Zheng, Hui; Smith, Roy G · Animal Study
Natriuretic peptide system physiology (ANP/BNP cardiac production, NPR-A/B/C receptors, clearance mechanisms) directly underlies their clinical utility for heart failure diagnosis, prognosis, population screening, and treatment monitoring.
Suttner, Stefan W; Boldt, Joachim · Review
Mice engineered without the vasopressin V1b receptor had significantly lower baseline levels of both ACTH and corticosterone — the key hormones that drive the body's stress response. When stressed (forced swimming), these knockout mice showed a blunted ACTH surge compared to normal mice. The V1b receptor responds to vasopressin but not to CRH (corticotropin-releasing hormone), confirming that vasopressin's stress-axis effects work through a distinct pathway. Critically, the V1b receptor wasn't just important during stress — it also maintained baseline hormone levels under resting conditions. This means vasopressin isn't just a stress-response amplifier; it's an essential regulator of the entire HPA axis at all times.
Tanoue, Akito; Ito, Shuji; Honda, Kenji; Oshikawa, Sayuri; Kitagawa, Yoko; Koshimizu, Taka-Aki; Mori, Toyoki; Tsujimoto, Gozoh · Animal Study
H. pylori infection significantly altered gastric ghrelin mRNA and protein expression, with changes correlating with infection severity and potentially explaining H. pylori-associated appetite changes and the weight gain often seen after eradication treatment.
Tatsuguchi, Atsushi; Miyake, Kazumasa; Gudis, Katya; Futagami, Seiji; Tsukui, Taku; Wada, Ken; Kishida, Teruyuki; Fukuda, Yuh; Sugisaki, Yuichi; Sakamoto, Choitsu · Cross Sectional
BPC-157 produced region-specific changes in brain serotonin synthesis measured by alpha-methyl-L-tryptophan autoradiography — increasing synthesis in some regions while decreasing it in others, providing the serotonergic basis for its mood-modulating properties.
Tohyama, Y; Sikirić, P; Diksic, M · Animal Study
Lactoferricin B inhibited DNA, RNA, and protein synthesis in E. coli and B. subtilis at sub-MIC concentrations, demonstrating an intracellular mechanism of antimicrobial action complementing its known membrane-disrupting activity.
Ulvatne, Hilde; Samuelsen, Ørjan; Haukland, Hanne H; Krämer, Manuela; Vorland, Lars H · In Vitro
Lactoferrampin, a novel antimicrobial peptide from the N1-domain of bovine lactoferrin (distinct from lactoferricin in the N-lobe), showed broad antimicrobial activity — expanding the number of bioactive peptides derived from this single milk protein.
van der Kraan, Marieke I A; Groenink, Jasper; Nazmi, Kamran; Veerman, Enno C I; Bolscher, Jan G M; Nieuw Amerongen, Arie V · In Vitro
A hydrocarbon-stapled BH3 alpha-helix peptide activated apoptosis in vivo in a mouse leukemia model, producing tumor reduction — the first demonstration that stapled peptide technology achieves in-vivo anticancer efficacy through intracellular target engagement.
Walensky, Loren D; Kung, Andrew L; Escher, Iris; Malia, Thomas J; Barbuto, Scott; Wright, Renee D; Wagner, Gerhard; Verdine, Gregory L; Korsmeyer, Stanley J · Animal Study
Endogenous opioid peptides have extensive non-opioid receptor activities: immune modulation, cell proliferation control (via OGFr), cardiovascular protection, neuroprotection, and antimicrobial effects — mediated through non-classical receptors and direct physicochemical mechanisms.
Wollemann, Mária; Benyhe, Sándor · Review
NT-proCNP (endothelial origin, unlike cardiac ANP/BNP) was elevated in heart failure and correlated with severity, providing a biomarker reflecting vascular endothelial dysfunction to complement cardiac-derived natriuretic peptides.
Wright, Sue P; Prickett, Tim C R; Doughty, Robert N; Frampton, Chris; Gamble, Greg D; Yandle, Tim G; Sharpe, Norman; Richards, Mark · Cohort
High-dose IT morphine produced anti-analgesia mediated by spinal dynorphin release and NMDA receptor activation (blocked by MK-801 and anti-dynorphin), demonstrating a universal opioid-induced hyperalgesia mechanism across both synthetic and endogenous opioids.
Wu, Hsiang-En; Thompson, Jonathan; Sun, Han-Sen; Leitermann, Randy J; Fujimoto, James M; Tseng, Leon F · Animal Study
Gut hormones (GLP-1, PYY, ghrelin, CCK, oxyntomodulin) regulate body weight through coordinated appetite and energy expenditure signaling, with GLP-1 receptor agonists showing the most advanced clinical development for obesity treatment.
Wynne, Katie; Stanley, Sarah; Bloom, Steve · Review
BPC-157 healed gastric ulcers in multiple rat models through comprehensive mechanisms: promoted angiogenesis, reduced inflammation, enhanced cytoprotection, and accelerated mucosal regeneration — acting through pathways independent of acid secretion reduction.
Xue, Xiao-Chang; Wu, Yong-Jie; Gao, Ming-Tang; Li, Wen-Guang; Zhao, Ning; Wang, Zeng-Lu; Bao, Chun-Jie; Yan, Zhen; Zhang, Ying-Qi · Animal Study
In-vitro GHRP-2 treatment altered pituitary somatotroph expression of GH, Pit-1 transcription factor, GHRH-R, and GHS-R at mRNA and protein levels, demonstrating GH secretagogue-induced pituitary cell reprogramming for enhanced GH-axis responsiveness.
Yan, Ming; Hernandez, Maria; Xu, Ruwei; Chen, Chen · In Vitro
Natriuretic peptides (BNP, NT-proBNP) are clinically useful for distinguishing cardiac from respiratory causes of dyspnea, diagnosing pulmonary hypertension, and monitoring right ventricular function in patients with chronic respiratory disease.
Yap, Lok Bin; Mukerjee, Dev; Timms, Peter M; Ashrafian, Houman; Coghlan, John Gerard · Review
MD simulations showed bovine lactoferricin transforms from alpha-helix to beta-sheet at membrane surfaces, with the sheet conformation enabling deep membrane penetration — revealing the dynamic structural basis for its antimicrobial membrane disruption.
Zhou, Ning; Tieleman, D Peter; Vogel, Hans J · In Vitro
Long-term GHRP-2 treatment in GHRH knockout mice maintained GH secretion and body composition effects, demonstrating that GH secretagogues can sustainably stimulate GH through GHRH-independent pathways — important for conditions with GHRH deficiency.
Alba, Maria; Fintini, Danilo; Bowers, Cyril Y; Parlow, A F; Salvatori, Roberto · Animal Study
Short synthetic peptides derived from allergens — corresponding to T-cell epitopes — can induce immune tolerance without triggering the dangerous IgE-mediated allergic reactions that plague traditional whole-allergen immunotherapy ('allergy shots'). Because these peptide fragments are too small to cross-link the IgE antibodies on mast cells and basophils, they avoid triggering systemic allergic reactions while still teaching the immune system to tolerate the allergen. Recent clinical trial data indicates that these peptide vaccines work by inducing or expanding a population of antigen-specific regulatory T-cells, which actively suppress the allergic immune response. The same epitope-specific approach also shows promise for treating autoimmune diseases.
Ali, F Runa; Larché, Mark · Review
C12-alkyl chain coupling to a lactoferricin-derived peptide enhanced LPS neutralization by over 10-fold while maintaining antimicrobial activity, creating a dual-function peptide that both kills bacteria and neutralizes their toxic products.
Andrä, Jörg; Lohner, Karl; Blondelle, Sylvie E; Jerala, Roman; Moriyon, Ignacio; Koch, Michel H J; Garidel, Patrick; Brandenburg, Klaus · In Vitro
GHK peptide incorporated into a biotinylated collagenous wound dressing accelerated rat dermal wound healing: faster wound closure, enhanced granulation tissue formation, improved collagen deposition, and better overall histological healing scores versus scaffold alone.
Arul, V; Gopinath, D; Gomathi, K; Jayakumar, R · Animal Study
The endogenous peptide apelin powerfully improved heart function in mice without causing harmful heart enlargement. Acute injection increased ventricular elastance by 76% (from 3.7 to 6.5 mmHg/RVU, P=0.018) and nearly doubled preload recruitable stroke work (from 27.4 to 51.8, P=0.059). It also reduced left ventricular end diastolic area (P=0.006) and modestly increased heart rate (P=0.03). Chronic 14-day infusion increased cardiac output by 76% (from 0.142 to 0.25 L/min, P=0.001) and circumferential shortening velocity (P=0.049). Critically, post-mortem analysis showed no cardiac hypertrophy — heart weights and cell sizes were identical between apelin and control groups. The apelin receptor (APJ) was found throughout the adult mouse heart and was expressed in embryonic myocardium as early as day 13.5.
Ashley, Euan A; Powers, Jennifer; Chen, Mary; Kundu, Ramendra; Finsterbach, Tom; Caffarelli, Anthony; Deng, Alicia; Eichhorn, Jens; Mahajan, Raina; Agrawal, Rani; Greve, Joan; Robbins, Robert; Patterson, Andrew J; Bernstein, Daniel; Quertermous, Thomas · Animal Study