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B7-33 peptides are Synthesized and Lyophilized in the USA.
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FREE - 30ml bottle of bacteriostatic water
(Required for reconstitution)
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What is the B7-33 Peptide?
B7-33 is a soluble synthetic single-chain peptide obtained from the larger, naturally occurring protein H2-relaxin, which has pleiotropic actions impacting the musculoskeletal system, cardiovascular system, and reproduction. B7-33 appears to retain the anti-fibrotic properties of Relaxin without enhancing cAMP production, it may also stimulate ERK1/2 phosphorylation, and promote matrix metalloproteinase 2 (MMP2) expression and the degradation of extracellular collagen. The Relaxin family of peptides have four endogenous receptors divided into two pairs (RXFP1/2 and RXFP3/4). The function of these receptors are under scientific study, with researchers theorizing that:
RXFP-1: Influences sperm motility, pregnancy, vascular endothelium, and joint health.
RXFP-2: Affects testicular descent.
RXFP-3: Mutations of this receptor affect schizotypal personality disorder and certain sleep disturbances.
RXFP-4: The role of this receptor is not clear. It is known to be expressed on sperm and alters insulin-like peptide 5, which in turn regulates hunger/satiation signaling.
The Relaxin receptors appear to be stimulated by cAMP, orexin, corticotropin-releasing factor (CRF), several insulin-like peptides, and GLP-1. The agonists have been observed to exhibit anti-inflammatory, antioxidant, and wound healing properties. Research suggests that Relaxin has all the properties apart from vasodilator, blood vessel growth stimulator, and antihypertrophic. Therefore, the peptide and its derivatives may be useful in acute heart failure and other fibrotic disorders.
AKA: (B7-33)H2, GTPL9321
B7-33 Peptide Function
B7-33 appears to preferentially stimulate the pERK pathway over the cAMP pathway. The pERK pathway regulates cell cycle arrest in the G1 phase and has been implicated in several diseases like Alzheimer’s and Crutzfeld-Jacob. By blocking cell cycle progression in cells with RXFP1 receptors, B7-33 appears to exercise anti-fibrotic effects through the ability to stimulate RXFP1-angiotensin II type 2 receptor heterodimering, which activates pERK1/2 signaling and thus triggers the increased production of the collagen-degrading enzyme matrix metalloproteinase (MMP) -2.
B7-33 and Ease of Production
B7-33 is easier to produce and is more economical. It has less complicated 2D and 3D structures; it is easier to produce a functional B7-33 protein than a full H2-relaxin protein.
B7-33 and Anti-Fibrotic Properties
Fibrosis involves scarring or unorganized tissue regeneration and is the end state of at least half of all chronic diseases. In 2012, H2-relaxin completed phase II clinical trials to treat acute heart failure. The research suggested that H2-relaxin administration may lead to instant vasodilation and reduces the long-term scarring seen following heart damage. Using the full relaxin protein as a therapeutic agent is challenging. H2-relaxin is difficult to produce and can only be administered via IV. It also appears to increase heart rate and may promote cancer progression (particularly prostate cancer). B7-33 peptide is under study for its potential to increase MMP-2 production slightly more than H2-relaxin does. This effect was noted in research studies, observing that the peptide appeared to significantly reduce cardiac fibrosis in rat models of MI-induced heart failure and improve cardiac function. Similar effects have been observed in mouse models of asthma and lung fibrosis. Further, B7-33 appeared to overcome tumor growth even when administered at higher doses than those producing anti-fibrotic effects. It appears to work almost exclusively through the pERK pathway without stimulating cAMP production.
B7-33 and Blood Vessel Protection
Human relaxin-2 (Serelaxin) has been studied for its potential to protect the vasculature against endothelial dysfunction and long-term scarring. B7-33 appears to replicate the vasoprotective effects of Serelaxin by enhancing bradykinin-mediated endothelium-dependent relaxation in arteries by boosting endothelium-derived hyperpolarization in certain vascular beds. Marshal et al. outlines that “equimolar doses of B7-33 replicated the acute beneficial vascular effects of serelaxin in rat mesenteric arteries and also prevented endothelial dysfunction induced by placental trophoblast conditioned media in mouse mesenteric arteries.” The apparent selectivity of this molecule in causing vasorelaxation may be useful in certain cardiovascular conditions and preeclampsia during pregnancy.
B7-33 and Preeclampsia
Preeclampsia is a common complication of pregnancy that leads to high blood pressure and reduced fetal weight. While manageable to a large degree, preeclampsia can be difficult to control and, in some cases, life-threatening to both mother and fetus. In the most extreme cases of preeclampsia, immediate delivery of the baby is necessary, making it a common cause of pre-term delivery. Research, however, suggests that Relaxin and its analogs (B7-33) may prove useful in controlling preeclampsia even in severe cases. B7-33 appears to bind to the RXFP-1 receptor, increasing VEGF production in cytotrophoblasts. These cells, found in the developing fetus, are crucial to establishing blood flow between the maternal circulation and the developing fetus. By triggering VEGF production, B7-33 has the potential to promote the growth of blood vessels and thus improve the blood supply between mother and child. Studies observe that lipidated B7-33 appears to have a prolonged in vivo half-life and that lipidation does not affect the activity of the peptides. A longer half-life would make B7-33 an even more effective therapeutic.
B7-33 and Anti-Fibrotic Materials
B7-33 appears to find application in producing anti-fibrotic materials or materials that resist the foreign body response. Fibrosis becomes problematic for implanting a medical device, like a cardiovascular stent, into the body. In these cases, fibrosis can lead to dysfunction or degradation of the implant and even lead to artery occlusion, reduced blood supply, and eventually a heart attack. There is potential for B7-33 to offer an ideal coating for use in implants. Research has observed that the release of B7-33 from the coating of a device appeared to reduce fibrotic capsule thickness by nearly 50% over a 6-week trial, and opened up the possibility of a range of improved implantable medical devices. The use of B7-33 and similar peptides may avoid the use of systemic substances to reduce fibrosis of implanted medical devices. This reduction would make the devices safer and allow them to be implanted in a wider range of patients with more severe diseases.
B7-33 is a novel peptide with apparently potent anti-fibrotic effects. It is actively studied for its potential to reduce fibrosis in acute and chronic diseases like heart failure and lung inflammation. The peptide has appeared to reduce fibrosis by roughly 50% in animal studies, leading to prolonged survival following injury and one of the first few offerings for treating heart failure in 20 years. The peptide holds the potential to reduce fibrosis and the rejection of implanted medical devices. Further, the B7-33 peptide appears to reduce blood pressure and protect vasculature. Studies in animal models of preeclampsia suggest that the peptide might be useful in treating this difficult-to-manage disease, potentially allowing more women to carry children to term in a safe manner for both mother and baby.
- Praveen, P., Kocan, M., Valkovic, A., Bathgate, R., & Hossain, M. A. (2019). Single chain peptide agonists of relaxin receptors. Molecular and cellular endocrinology, 487, 34-39.
- Yegorov, S., Bogerd, J., & Good, S. V. (2014). The relaxin family peptide receptors and their ligands: new developments and paradigms in the evolution from jawless fish to mammals. General and comparative endocrinology, 209, 93–105. https://doi.org/10.1016/j.ygcen.2014.07.014
- Hossain, M. A., Kocan, M., Yao, S. T., Royce, S. G., Nair, V. B., Siwek, C., Patil, N. A., Harrison, I. P., Rosengren, K. J., Selemidis, S., Summers, R. J., Wade, J. D., Bathgate, R. A. D., & Samuel, C. S. (2016). A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1. Chemical science, 7(6), 3805–3819. https://doi.org/10.1039/c5sc04754d
- Teerlink, J. R., Cotter, G., Davison, B. A., Felker, G. M., Filippatos, G., Greenberg, B. H., Ponikowski, P., Unemori, E., Voors, A. A., Adams, K. F., Jr, Dorobantu, M. I., Grinfeld, L. R., Jondeau, G., Marmor, A., Masip, J., Pang, P. S., Werdan, K., Teichman, S. L., Trapani, A., Bush, C. A., … RELAXin in Acute Heart Failure (RELAX-AHF) Investigators (2013). Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet (London, England), 381(9860), 29–39. https://doi.org/10.1016/S0140-6736(12)61855-8
- Marshall, S. A., O’Sullivan, K., Ng, H. H., Bathgate, R. A. D., Parry, L. J., Hossain, M. A., & Leo, C. H. (2017). B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). European journal of pharmacology, 807, 190–197. https://doi.org/10.1016/j.ejphar.2017.05.005
- Afroze, S. H., Pantho, A. F., Sprague, D. C., Kuehl, T. J., Bathgate, R., Zawieja, D. C., … & Uddin, M. N. (2019). Abstract P3042: Novel Peptide B7-33 and It’s Lipidated Derivative Protect Cytotrophoblasts From Preeclampsia Phenotype in a Cellular Model of the Syndrome. Hypertension, 74(Suppl_1), AP3042-AP3042.
- Welch, N. G., Mukherjee, S., Hossain, M. A., Praveen, P., Werkmeister, J. A., Wade, J. D., … & Thissen, H. (2019). Coatings releasing the relaxin peptide analogue B7-33 reduce fibrotic encapsulation. ACS applied materials & interfaces, 11(49), 45511-45519.
Dr. Usman (BSc, MBBS, MaRCP) completed his studies in medicine at the Royal College of Physicians, London. He is an avid researcher with more than 30 publications in internationally recognized peer-reviewed journals. Dr. Usman has worked as a researcher and a medical consultant for reputable pharmaceutical companies such as Johnson & Johnson and Sanofi.
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