| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Staphylococcus aureus[1]
RIP targets the quorum sensing system of S. aureus, specifically the RAP (RNAIII-activating protein)/TRAP (target of RAP) signaling pathway. It binds to TRAP, a 21-kDa protein, thereby preventing its phosphorylation and subsequent activation of the agr (accessory gene regulator) system. This inhibits the production of RNAIII, the regulatory RNA that controls expression of multiple virulence factors including alpha-toxin, Panton-Valentine leukocidin, and various exoproteins. |
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| ln Vitro |
Staphylococcus aureus is effectively inhibited by RNAIII-inhibiting peptide (TFA). While RAP activates in wild type S, RNAIII-inhibiting peptide (RIP) suppresses the synthesis of both RNAII and RNAIII. cells of aureus. In the absence of serum, RNAIII-inhibiting peptide (5 μg/106 cells) significantly decreases bacterial cell adhesion to HEp2 cells, while in the presence of serum, this reduction is just marginal. RAP phosphorylates TRAP while RNAIII-inhibiting peptide inhibits it[1].
In vitro, RIP at concentrations of 1-20 uM inhibits the production of RNAIII in S. aureus, leading to reduced expression of virulence factors such as hemolysins, proteases, and toxic shock syndrome toxin. RIP does not inhibit bacterial growth (MIC >256 ug/mL), which reduces selective pressure for resistance. It also inhibits biofilm formation in methicillin-resistant S. aureus (MRSA) and prevents the transition from a commensal to a pathogenic state. |
| ln Vivo |
In mice challenged with S, RNAIII-inhibiting peptide (20 mg/kg, iv) reduces lethality. fatality rate of 70% for aureus ATCC 25923, which drops to 20%, 15%, and 10% when cefazolin, imipenem, and vancomycin are added. In mice challenged with S, RNAIII-inhibiting peptide (20 mg/kg, iv) also reduces lethality. cefazolin, imipenem, and vancomycin reduce the fatality rate of aureus Smith, which is 75%, to 30%, 10%, and 10%, respectively[2].
In animal models, RIP (5-20 mg/kg, intraperitoneally or subcutaneously) has shown efficacy. In a mouse model of S. aureus-induced septic arthritis, RIP treatment reduced joint swelling, bacterial load, and mortality. In a rat model of implant-associated biofilm infection, RIP combined with vancomycin eradicated biofilms more effectively than vancomycin alone. In a murine wound infection model, topical RIP reduced bacterial spread and tissue damage. |
| Enzyme Assay |
For binding assays (surface plasmon resonance): Immobilize recombinant TRAP protein on a CM5 sensor chip. Flow increasing concentrations of RIP (0.1-50 uM) in HBS-EP buffer (10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.005% Tween-20, pH 7.4) over the chip at 25degC. Record association and dissociation phases. Calculate KD using BIAevaluation software. For phosphorylation inhibition assays, incubate TRAP with 14C-labeled RIP and measure TRAP phosphorylation by autoradiography.
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| Cell Assay |
For inhibition of RNAIII production: Culture S. aureus (e.g., RN6390 or clinical MRSA isolates) in TSB medium to mid-log phase. Add RIP (1, 5, 10, 20 uM) and incubate for 4-6 hours. Extract total RNA and perform Northern blotting or qRT-PCR using probes specific for RNAIII. For hemolysin production, culture bacteria overnight, centrifuge, and add supernatant to rabbit red blood cells; measure hemoglobin release at 540 nm. For biofilm assays, grow bacteria in microtiter plates with RIP (10-50 uM) for 24 h, stain with crystal violet, and measure OD570.
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| Animal Protocol |
For mouse septic arthritis model: Inject 2×10⁷ CFU of S. aureus (e.g., strain LS-1) intravenously into 8-10 week old female BALB/c mice. Administer RIP (5 mg/kg) or vehicle (PBS) intraperitoneally starting 2 days before infection and then daily for 10 days. Monitor clinical score of arthritis (0-3 per paw) and weight loss daily. On day 12, euthanize mice and collect kidneys, joints, and blood for bacterial CFU counts. Histological analysis of joints for inflammation and cartilage destruction.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is available for RIP in humans. In mice, intraperitoneal administration of 5 mg/kg RIP leads to peak plasma concentrations within 30-60 minutes with a half-life of approximately 2-4 hours. RIP is a peptide and is subject to proteolytic degradation; it is cleared primarily by the kidneys. Its short half-life may require frequent dosing. PEGylation or formulation in depots has been explored to improve PK.
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| Toxicity/Toxicokinetics |
In animal studies, RIP has demonstrated a very favorable toxicity profile. At doses up to 50 mg/kg (i.p.) daily for 14 days, no significant weight loss, organ toxicity, or behavioral changes were observed in mice. RIP does not kill bacteria, so it does not induce endotoxin release or disruption of the microbiome. It is not cytotoxic to mammalian cells at concentrations up to 100 uM. However, clinical safety in humans is unknown.
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| References |
[1]. Gov Y, et al. RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: structure and function analysis. Peptides. 2001 Oct;22(10):1609-20.
[2]. Giacometti A, et al. RNAIII-inhibiting peptide improves efficacy of clinically used antibiotics in a murine model of staphylococcal sepsis. Peptides. 2005 Feb;26(2):169-75 |
| Additional Infomation |
RNAIII-inhibiting peptide (RIP) is a research compound that has not been approved for clinical use. It has been evaluated in phase I/II clinical trials for reducing S. aureus colonization and infections, but development has not progressed to market. The peptide is supplied as a TFA salt, lyophilized powder. Store at -20degC desiccated. It is soluble in water, PBS, and DMSO. For research use only, not for human therapy.
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| Molecular Formula |
C47H57F3N10O13
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|---|---|
| Molecular Weight |
1027.01
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| Exact Mass |
1026.405
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| CAS # |
2703745-76-8
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| PubChem CID |
134128288
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
13
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
73
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| Complexity |
1790
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| Defined Atom Stereocenter Count |
8
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| SMILES |
FC(C(=O)O)(F)F.O=C([C@@H]1CCCN1C([C@H](CO)NC([C@H](CC1C=CC(=CC=1)O)N)=O)=O)N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N)=O)CC1C=CC=CC=1)=O)CC(N)=O)=O)[C@@H](C)O)=O)CC1=CNC2C=CC=CC1=2
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| InChi Key |
UFMWBLWECSYAKK-TUPMYQNZSA-N
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| InChi Code |
InChI=1S/C45H56N10O11.C2HF3O2/c1-24(57)38(44(65)52-34(21-37(47)59)41(62)50-32(39(48)60)19-25-8-3-2-4-9-25)54-42(63)33(20-27-22-49-31-11-6-5-10-29(27)31)51-43(64)36-12-7-17-55(36)45(66)35(23-56)53-40(61)30(46)18-26-13-15-28(58)16-14-26;3-2(4,5)1(6)7/h2-6,8-11,13-16,22,24,30,32-36,38,49,56-58H,7,12,17-21,23,46H2,1H3,(H2,47,59)(H2,48,60)(H,50,62)(H,51,64)(H,52,65)(H,53,61)(H,54,63);(H,6,7)/t24-,30+,32+,33+,34+,35+,36+,38+;/m1./s1
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| Chemical Name |
(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]butanediamide;2,2,2-trifluoroacetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 150 mg/mL (146.06 mM)
H2O : 100 mg/mL (97.37 mM) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9737 mL | 4.8685 mL | 9.7370 mL | |
| 5 mM | 0.1947 mL | 0.9737 mL | 1.9474 mL | |
| 10 mM | 0.0974 mL | 0.4869 mL | 0.9737 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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