tnf-a-in-6

Mca-(endo-1a-Dap(Dnp))-TNF-Alpha (-5 to +6) amide (human) is a peptide used as a fluorescence resonance energy transfer (FRET) based substrate for proteolytic activity assays, with cleavage-induced changes in fluorescence intensity indicating enzymatic activity [1].

Interphotoreceptor retinoid-binding protein (651-670) (IRBP651-670), a peptide fragment of retinoid-binding protein 3 (also known as IRBP), plays a crucial role in the visual cycle by facilitating the transport of retinol and retinal between photoreceptor cells and the retinal pigment epithelium. This transport is essential for the regeneration of pigments necessary for vision. When administered at a dose of 300 µg/animal, IRBP651-670 induces autoimmune uveoretinitis in C57BL/6 mice, a model possessing the H-2b haplotype. This immunization leads to increased levels of ocular cytokines including IL-1β, IL-6, IL-17, TNF-α, and IFN-γ, promotes immune cell infiltration into the eye, and results in photoreceptor cell damage.

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.1It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).2α-MSH (100 pM) reducesS. aureuscolony formation andC. albicansgerm tube formationin vitro.3It inhibits endotoxin-, ceramide-, TNF-α-, or okadaic acid-induced activation of NF-κB in U937 cells.1α-MSH reduces IL-6- or TNF-α-induced ear edema in mice.4It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of α-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.1 1.Catania, A., Airaghi, L., Colombo, G., et al.α-melanocyte-stimulating hormone in normal human physiology and disease statesTrends Endocrinol. Metab.11(8)304-308(2000) 2.Miwa, H., Gantz, I., Konda, Y., et al.Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptorsJ. Pharmacol. Exp. Ther.273(1)367-372(1995) 3.Cutuli, M., Cristiani, S., Lipton, J.M., et al.Antimicrobial effects of a-MSH peptidesJ. Leukoc. Biol.67(2)233-239(2000) 4.Lipton, J.M., Ceriani, G., Macaluso, A., et al.Antiiinflammatory effect of the neuropeptide a-MSH in acute, chronic, and systemic inflammationAnn. N.Y. Acad. Sci.25(741)137-148(1994)

PapRIV, a quorum-sensing heptapeptide derived from B. cereus, undergoes synthesis as a 48-amino acid polypeptide. This compound is secreted and then extracellularly processed by NprB proteases into its active form. At concentrations ranging from 1-25 µM, PapRIV triggers the production of IL-6 and TNF-α, as well as NF-κB translocation, specifically in BV-2 microglia cells.

Cathelicidin-2 (CATH-2) (128-153) is a synthetic antimicrobial peptide derived from amino acids 128-153 of chicken CATH-2, demonstrating activity against pathogens such as E. coli, S. aureus, S. enteritidis, and B. globigii in a dose-dependent manner. At a concentration of 40 µM, it induces hemolysis in chicken erythrocytes without exhibiting cytotoxicity towards human peripheral blood mononuclear cells (PBMCs). Additionally, it stimulates the production of the chemokine CCL2 and suppresses LPS-induced secretion of TNF-α, IL-6, IL-8, and IL-10 in human PBMCs.

F1, an anti-inflammatory peptide, incorporates the HIV-1 Tat protein transduction domain linked with a 15-amino acid sequence from residues 46-60 of the inhibitor of NF-κB kinase-interacting peptide (IKIP). It effectively blocks LPS-induced phosphorylation of IκB kinase α (IKKα) and IKKβ, along with the nuclear translocation of NF-κB (p65) in mouse peritoneal macrophages at 5 µM concentration. F1, administered at 5 mg/kg in vivo, significantly reduces IL-6, TNF-α, and IL-1β serum levels and enhances survival in a mouse sepsis model induced by LPS.

NCI 126224, a toll-like receptor 4 (TLR4) antagonist, demonstrates selective inhibition of nitric oxide (NO) production in RAW 264.7 macrophages, triggered by the TLR4 agonist LPS (IC50 = 0.31 µM), as opposed to minimal effects on NO production induced by agonists for TLR7/8 (R-848), TLR1/2 (Pam3CSK4), and TLR3 (poly(I:C)). Nevertheless, it also effectively inhibits NO production initiated by the TLR2/6 agonist FSL-1 at an IC50 of 0.6 µM in the same cell line. Moreover, NCI 126224 suppresses LPS-induced NF-κB activity in BV-2 microglial cells and reduces LPS-triggered increases in IL-1β and TNF-α levels in RAW 264.7 macrophages with IC50 values of 5.92, 0.42, and 1.54 µM, respectively.

Pap12-6, an antibacterial peptide originating from the first twelve N-terminal amino acids of papiliocin found in P. xuthus larvae, exhibits activity against a range of eight Gram-negative bacteria (e.g., E. coli, P. aeruginosa, S. syphimurium with MIC50s=4-8 µM) and Gram-positive bacteria (e.g., S. aureus, methicillin-resistant S. aureus 3126, B. subtilis, and S. epidermidis with MIC50s=4-8 µM), without compromising the viability of human erythrocytes, mouse RAW 264.7 macrophages, human HaCaT keratinocytes, or human HEK293 kidney cells at 25 µM. It causes membrane depolarization in E. coli at 4 and 8 µM and, upon preincubation at 10 µM, decreases nitrite (NO2-), Tnf-α, and Il-6 secretion in LPS-stimulated RAW 264.7 macrophages. In a murine model, Pap12-6 enhances survival rates and diminishes colony forming units (CFUs) in several organs upon E. coli infection at 10 mg/kg and 1 mg/kg doses, respectively. Additionally, at a 1 mg/kg dose, it lowers serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels, as well as blood urea nitrogen levels in E. coli-induced sepsis, indicating its therapeutic potential for bacterial infections without affecting host cell viability.

Trofinetide, derived from the neuroprotective tripeptide Gly-Pro-Glu (an N-terminal sequence of insulin-like growth factor-1, IGF-1), shows promise in various neuroprotective models. At a concentration of 10 nM, it mitigates cell death in primary rat embryonic striatal neurons caused by okadaic acid. Additionally, Trofinetide reduces the expression of pro-inflammatory markers (IL-1β, TNF-α, IL-6, and E-selectin) in a rat model simulating neuroinflammation from penetrating ballistic-like brain injuries. In cases of brain injury induced by middle cerebral artery occlusion (MCAO), administration of Trofinetide at 30 and 60 mg/kg reduces the area of cortical and striatal infarct. Furthermore, a daily dose of 100 mg/kg reverses social recognition and contextual fear conditioning deficits, diminishes the number of dendritic spines, and decreases testicular weight gain in an fmr1-/- knockout mouse model of fragile X syndrome. Trofinetide formulations have been employed in treating Rett syndrome, highlighting its versatility across various neurological conditions.

TLR2/6 agonist (also a putative TLR10 ligand). Activates NF-κB. Induces pro-inflammatory cytokines including IL-8, IL-1β, CCL20 and TNF-α in vitro. Synergizes with IFNγ to induce CXCL10 release from melanoma cells.

PMX-53, a macrocyclic complement 5a (C5a) peptidomimetic and C5a receptor antagonist (IC50 = 0.3 µM), effectively inhibits the C5a-induced secretion of myeloperoxidase (MPO) in isolated human polymorphonuclear leukocytes (PMNs). Administered orally at 10 mg/kg, PMX-53 mitigates vascular leakage, PMN infiltration, and the production of TNF-α and IL-6 in a rat peritoneal Arthus reaction model. Additionally, in a 3-nitropropionic acid (3-NP)-induced Huntington’s disease rat model, it alleviates body weight loss, anorexia, and striatal degeneration. Furthermore, at a dose of 3 mg/kg, PMX-53 decreases atherosclerotic lesion size and lipid content in ApoE-/- mice.