![β-Sheet Breaker Peptide iAβ5 ([Pro18, Asp21] β-Amyloid (17-21))](/upload/1124/V71366.png)
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| Targets |
The primary target of iAbeta5 is the beta-sheet conformation of aggregated amyloid-beta (Abeta). The peptide binds to the hydrophobic core of Abeta fibrils, acting as a beta-sheet breaker that destabilizes the intermolecular beta-sheet structure of amyloid deposits. By interacting with the self-recognition element of Abeta, iAbeta5 induces the disaggregation of preformed fibrils and prevents the formation of new beta-sheet-rich toxic oligomers. This mechanism reduces both amyloid plaque burden and associated neuroinflammation.
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| ln Vitro |
β-Sheet Breaker Peptide iAβ5 (1.5 μg/μL; 7 days) suppresses the development of amyloid beta fibrils, degrades preexisting fibrils in vitro, and shields cell culture neurons from fibril-induced mortality [1]. Following a two-day treatment with 50 μM aggregated Aβ1-42 in human neuroblastoma (IMR-32) cells, β-Sheet Breaker Peptide iAβ5 (60 μM; 48 hours) demonstrated no cytotoxicity [1].
In vitro, iAbeta5 functions as a potent beta-sheet breaker that binds to aggregated Abeta fibrils. The amino acid substitutions (Pro18 and Asp21) prevent the peptide from adopting a beta-sheet conformation while maintaining high affinity for the target fibrils. Through hydrophobic interactions, iAbeta5 disrupts the intermolecular beta-sheet structure of Abeta aggregates, inducing their disassembly into smaller, less toxic fragments. This activity is concentration-dependent and has been demonstrated in both synthetic Abeta fibrils and brain-derived amyloid deposits. |
| ln Vivo |
Aβ1-42 (5 nmol) was co-injected into the rat amygdala along with β-Sheet Breaker Peptide iAβ5 (100 nmol/rat; intra-amygdala injection; 7 days) to prevent Aβ1-42 neurotoxicity in tissue culture. as well as the rat models' development of amyloid fibrils [1]. When administered intraamygdally seven days after treatment with Aβ1-42 (5 nmol), β-Sheet Breaker Peptide iAβ5 (100 nmol/rat, 200 nmol/rat; intra-amygdala injection) causes the body's pre-existing Aβ fibrils to break down, which in turn reverses or prevents Aβ-induced histopathological alterations in rat models [2].
In vivo, beta-Sheet Breaker Peptide iAbeta5 is a potent degrader of cerebral amyloid-beta (Abeta). It crosses the blood-brain barrier (BBB) at a higher rate than most known proteins and peptides and is selectively absorbed by the brain. When administered systemically or intracerebrally to transgenic mouse models of Alzheimer's disease, iAbeta5 induces the reproducible decomposition of fibrillar amyloid deposits, prevents or reverses Abeta-induced neuronal atrophy, and reduces the area of IL-1beta-positive microglial cells surrounding Abeta deposits. |
| Enzyme Assay |
iAbeta5 activity is assessed using a thioflavin T (ThT) fluorescence assay. Synthetic Abeta1-42 (25 uM) is pre-incubated at 37degC for 24-72 hours to allow fibril formation. Varying concentrations of iAbeta5 (e.g., 1-100 uM) are then added to the pre-formed fibrils, and the mixture is incubated for an additional 24-48 hours. ThT is added, and fluorescence (excitation 440 nm, emission 485 nm) is measured. A decrease in ThT fluorescence relative to Abeta alone indicates fibril disassembly by iAbeta5.
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| Cell Assay |
For cellular assays, primary cortical neurons or neuroblastoma cells (e.g., SH-SY5Y) are exposed to pre-formed Abeta42 fibrils (10 uM) for 24 hours to induce neurotoxicity. In a second group, iAbeta5 (e.g., 10-50 uM) is co-incubated with the Abeta fibrils prior to addition to the cells. After 24-48 hours, cell viability is assessed by MTT or LDH release. Protection against Abeta-induced cell death confirms the neuroprotective activity of iAbeta5 through fibril disassembly.
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| Animal Protocol |
beta-Sheet Breaker Peptide iAbeta5 crosses the blood-brain barrier faster than most known proteins and peptides, and it is selectively absorbed by the brain. A typical protocol uses the APP/PS1 double transgenic mouse model of Alzheimer‘s disease. iAbeta5 is administered intraperitoneally (e.g., 10 mg/kg/day) or via intracerebroventricular infusion (e.g., 5-20 microg/day) for 2-4 weeks. Following treatment, mice are sacrificed, and brain sections are stained with Congo red, Thioflavin S, or 6E10 antibody to assess amyloid plaque burden. A reduction in plaque area and number indicates in vivo efficacy.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data for iAbeta5 is provided, but a key property is its ability to cross the blood-brain barrier at a higher rate than most known proteins and peptides. It is speculated that the peptide is specifically transported into the brain via a yet-unidentified transport mechanism. As a pentapeptide, iAbeta5 is susceptible to proteolytic degradation, but the substitution of natural L-amino acids may enhance its stability relative to the native Abeta fragment.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is provided for iAbeta5. In preclinical studies, beta-sheet breaker peptides have been reported to be well-tolerated at therapeutic doses. Potential adverse effects may include local injection site reactions (if administered ICV) or immune responses to peptide-based therapeutics. Standard laboratory safety precautions for handling peptides should be followed, and the compound is not intended for human use without appropriate safety testing.
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| References |
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| Additional Infomation |
beta-Sheet Breaker Peptide iAbeta5 is a unique research tool for Alzheimer's disease because it targets pre-formed amyloid aggregates for disassembly, rather than merely preventing their formation. The specific amino acid substitutions (Pro18, Asp21) are designed to prevent the peptide from adopting a beta-sheet conformation while retaining high affinity for Abeta fibrils. iAbeta5 has been studied as a potential anti-amyloid therapeutic, and its ability to cross the BBB more efficiently than most other peptides makes it a promising lead for AD drug development. The peptide is also used to reduce the size or number of amyloid plaques within the brain in research models of AD.
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| Molecular Formula |
C33H43N5O8
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| Molecular Weight |
637.72
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| Exact Mass |
637.311
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| CAS # |
182912-74-9
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| PubChem CID |
10146049
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| Appearance |
White to off-white solid powder
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| LogP |
2.66
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
46
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| Complexity |
1070
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CC(=O)O)C(=O)O)N
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| InChi Key |
RALAXQOLLAQGTI-IRGGMKSGSA-N
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| InChi Code |
InChI=1S/C33H43N5O8/c1-20(2)16-23(34)32(44)38-15-9-14-27(38)31(43)36-25(18-22-12-7-4-8-13-22)29(41)35-24(17-21-10-5-3-6-11-21)30(42)37-26(33(45)46)19-28(39)40/h3-8,10-13,20,23-27H,9,14-19,34H2,1-2H3,(H,35,41)(H,36,43)(H,37,42)(H,39,40)(H,45,46)/t23-,24-,25-,26-,27-/m0/s1
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| Chemical Name |
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]butanedioic 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
H2O: 50 mg/mL (78.40 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 | 1.5681 mL | 7.8404 mL | 15.6809 mL | |
| 5 mM | 0.3136 mL | 1.5681 mL | 3.1362 mL | |
| 10 mM | 0.1568 mL | 0.7840 mL | 1.5681 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05081401
Conditions:Multidrug Resistant Tuberculosis|Rifampicin Resistant Tuberculosis|Pre-XDR-TBLink: https://clinicaltrials.gov/ct2/show/NCT04261166
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