Apolipoprotein E fragment (133-149) – COG133: acetyl-LRVRLASHLRKLRKRLL-NH2 (CAS : 514200-66-9)

SB-PEPTIDE offers Apolipoprotein E (ApoE) mimetic peptide COG133 – LRVRLASHLRKLRKRLL – which competes with the ApoE holoprotein for binding the low density lipoprotein (LDL) receptor.

Apolipoprotein E (ApoE): A key player in lipid transport and beyond

Apolipoprotein E (apoE) is a low-density lipoprotein (LDL) receptor ligand that belongs to the family of fat-binding proteins, known as apolipoproteins. While the liver and macrophages primarily produce ApoE in peripheral tissues to mediate cholesterol metabolism, in the central nervous system (CNS), astrocytes take the lead in producing ApoE.

ApoE plays a vital role in lipid transport, facilitating the movement of lipids such as fats, cholesterol, and fat-soluble vitamins between organs via plasma and interstitial fluids. In the central CNS, it serves as a crucial cholesterol carrier, promoting neuron survival, sprouting, and exhibiting functional anti-inflammatory and neuroprotective effects.

Beyond its role in lipid transport, ApoE binds to a diverse range of cellular receptors, influencing immune responses, promoting cell migration, and potentially impacting transcription regulation.

With its multifaceted functions, ApoE stands as a cornerstone in maintaining plasma and tissue lipid homeostasis and orchestrating complex interplays within the body.

ApoE(133-149) mimetic peptide : COG 133

COG 133 mimetic peptide, takes the incredible capabilities of acting the same way as the LDL receptor-binding domain of ApoE. Therefore, this peptide wields a non-competitive stance against the alpha-7 nicotinic acetylcholine receptor, which is not only implicated in long-term memory but also in neurotoxicity, stroke, myocardial infarction, sepsis, Alzheimer’s disease, cancer progression, and angiogenic/neurogenic activity. Moreover, COG133’s anti-apoptotic effects further accentuate its potential.

By mimicking ApoE, COG 133 / ApoE(133-149) masterfully inhibits the NMDA receptor channel function through interactions with the low-density lipoprotein receptor-related protein. The peptide emerged as a potent agent in reducing inflammation, cellular infiltration, and demyelination, making strides in animal models of multiple sclerosis (MS) and the 5-fluorouracil model of intestinal mucositis.

Indeed, COG-133 emerged as a champion to suppress symptoms of experimental autoimmune encephalomyelitis (EAE), curbing inflammation, demyelination, and cell infiltration in the spinal cord. ApoE (133-149) fragment additionally showcased its prowess by decreasing TNF-α and nitric oxide (NO) release in BV-2 microglia and counteracting LPS-induced increases in brain levels of TNF-α and IL-6 in mice. The peptide also stands as a guardian of hippocampal neuronal health and offers promise in delaying disease onset and reducing severity of EAE mouse model.

COG-133 applications

The applications of COG 133 (ApoE 133-149) resonate across diverse fields of research and healthcare.

Generally speaking, COG133’s multifaceted influences on inflammation, cellular responses, and neuronal health open doors to novel therapies for neurological disorders.

Its potential as a groundbreaking tool in understanding and combating MS holds the promise of improved treatments and enhanced quality of life for patients suffering from this particular disease.

SB-PEPTIDE is proud to offer this remarkable peptide for neurological research!

Technical specification

	Sequence : acetyl-LRVRLASHLRKLRKRLL-NH2
	MW : 2169,72 g/mol (C₉₇H₁₈₁N₃₇O₁₉)
	Purity : > 95%
	Counter-Ion : TFA Salts (see option TFA removal)
	Delivery format : Freeze dried in propylene 2mL microtubes
	Other names : ApoE (133-149)
	Peptide Solubility Guideline
	Bulk peptide quantities available

Price

Product catalog	Size	Price € HT	Price $ USD
SB180-1MG	1 mg	121	151
SB180-5MG	5 mg	424	529
SB180-25MG	25 mg	1100	1375

References

Front. Cell Dev. Biol. 2021 Jan 08;8:621144. doi: https://doi.org/10.3389/fcell.2020.621144

ApoPred: Identification of Apolipoproteins and Their Subfamilies With Multifarious Features

Apolipoprotein is a group of plasma proteins that are associated with a variety of diseases, such as hyperlipidemia, atherosclerosis, Alzheimer’s disease, and diabetes. In order to investigate the function of apolipoproteins and to develop effective targets for related diseases, it is necessary to accurately identify and classify apolipoproteins. Although it is possible to identify apolipoproteins accurately through biochemical experiments, they are expensive and time-consuming. This work aims to establish a high-efficiency and high-accuracy prediction model for recognition of apolipoproteins and their subfamilies. We firstly constructed a high-quality benchmark dataset including 270 apolipoproteins and 535 non-apolipoproteins. Based on the dataset, pseudo-amino acid composition (PseAAC) and composition of k-spaced amino acid pairs (CKSAAP) were used as input vectors. To improve the prediction accuracy and eliminate redundant information, analysis of variance (ANOVA) was used to rank the features. And the incremental feature selection was utilized to obtain the best feature subset. Support vector machine (SVM) was proposed to construct the classification model, which could produce the accuracy of 97.27%, sensitivity of 96.30%, and specificity of 97.76% for discriminating apolipoprotein from non-apolipoprotein in 10-fold cross-validation. In addition, the same process was repeated to generate a new model for predicting apolipoprotein subfamilies. The new model could achieve an overall accuracy of 95.93% in 10-fold cross-validation. According to our proposed model, a convenient webserver called ApoPred was established, which can be freely accessed at http://tang-biolab.com/server/ApoPred/service.html. We expect that this work will contribute to apolipoprotein function research and drug development in relevant diseases.

Journal of Lipid Research. 2014 Aug 25;55(10):2007-2021. doi: https://doi.org/10.1194/jlr.r051367

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review.

Reduced levels of HDL cholesterol (HDL-C) are a strong independent predictor of coronary artery disease (CAD) risk. The major anti-atherogenic function of HDL is to mediate reverse cholesterol transport. This response is highly dependent on apoA-I and apoE, protein components of HDL. Randomized clinical trials have assessed effects of several classes of drugs on plasma cholesterol levels in CAD patients. Agents including cholestyramine, fibrates, niacin, and statins significantly lower LDL cholesterol (LDL-C) and induce modest increases in HDL-C, but tolerance issues and undesirable side effects are common. Additionally, residual risk may be present in patients with persistently low HDL-C and other complications despite a reduction in LDL-C. These observations have fueled interest in the development of new pharmacotherapies that positively impact circulating lipoproteins. The goal of this review is to discuss the therapeutic potential of synthetic apolipoprotein mimetic peptides. These include apoA-I mimetic peptides that have undergone initial clinical assessment. We also discuss newer apoE mimetics that mediate the clearance of atherogenic lipids from the circulation and possess anti-inflammatory properties. One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials.

ISRN Biochemistry. 2013 May 21;2013:238428. doi: https://doi.org/10.1155/2013/238428

Nanoparticles for brain drug delivery.

The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier (BBB) regulating its homeostasis. BBB is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the BBB. Within this review, the recently born strategy of brain drug delivery based on the use of nanoparticles, multifunctional drug delivery systems with size in the order of one-billionth of meters, is described. The review also includes a brief description of the structural and physiological features of the barrier and of the most utilized nanoparticles for medical use. Finally, the potential neurotoxicity of nanoparticles is discussed, and future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments.

Advanced Materials (Deerfield Beach, Fla.). 2011 Aug 15;23(36):H217-47. doi: https://doi.org/10.1002/adma.201102313

Cancer nanotheranostics: improving imaging and therapy by targeted delivery across biological barriers.

Cancer nanotheranostics aims to combine imaging and therapy of cancer through use of nanotechnology. The ability to engineer nanomaterials to interact with cancer cells at the molecular level can significantly improve the effectiveness and specificity of therapy to cancers that are currently difficult to treat. In particular, metastatic cancers, drug-resistant cancers, and cancer stem cells impose the greatest therapeutic challenge for targeted therapy. Targeted therapy can be achieved with appropriately designed drug delivery vehicles such as nanoparticles, adult stem cells, or T cells in immunotherapy. In this article, we first review the different types of nanotheranostic particles and their use in imaging, followed by the biological barriers they must bypass to reach the target cancer cells, including the blood, liver, kidneys, spleen, and particularly the blood-brain barrier. We then review how nanotheranostics can be used to improve targeted delivery and treatment of cancer cells. Finally, we discuss development of nanoparticles to overcome current limitations in cancer therapy.

The Journal of Pharmacology and Experimental Therapeutics. 2006 Jun 01;318(3):956-965. doi: https://doi.org/10.1124/jpet.106.103671

Apolipoprotein E-derived peptides ameliorate clinical disability and inflammatory infiltrates into the spinal cord in a murine model of multiple sclerosis.

Apolipoprotein E (apoE), well known to play a role in lipid transport and cholesterol metabolism, also exerts anti-inflammatory and neuroprotective effects in the central nervous system. Recent clinical and genetic studies display an association between apoE genotype (APOE) and the progression and severity of multiple sclerosis, raising the possibility that modulation of apoE may be a novel treatment for multiple sclerosis. Using a murine experimental autoimmune encephalomyelitis (EAE) model of human multiple sclerosis, we found that a peptidomimetic of apoE protein, COG133, substantially reduces the clinical symptoms of EAE and promotes remission from the disability when administered before or after onset of disease. Most notably, fusion of COG133 to a protein transduction domain creates COG112, a modified apoE-mimetic peptide with significantly enhanced anti-inflammatory bioactivities in vitro, and improved therapeutic effects on EAE in vivo, which renders a nearly full remission from the disability. Histopathological analysis showed that COG112 and COG133 attenuated demyelination and significantly diminished the number of peripheral cells infiltrating into the spinal cord. ApoE mimetics also interfered with several mechanisms relevant to the pathogenesis of EAE and multiple sclerosis, including activation of macrophages, subsequent production of nitric oxide and inflammatory cytokines, and lymphocyte proliferation. These data suggest that apoE mimetics represent a multidimensional therapeutic for multiple sclerosis capable of inhibiting the inflammatory cascade, modulating immune cell function, and reducing clinical signs, which may have novel utility for the treatment of inflammatory autoimmune diseases.

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