B7-33 (6mg)

B7-33 Peptide

H2-relaxin is a naturally occurring protein and the synthetic analog of this protein is the B7-33 peptide. Considered to be structurally similar to H2-relaxin, B7-33 may possess anti-fibrotic potential.

The H2-relaxin protein is a protein class comprised of relaxin, H3-relaxin, insulin-like peptide-3, and insulin-like peptide-5. All these proteins have been suggested to exhibit a variety of biological actions, including possibly affecting genetic functions and the reproductive, musculoskeletal, and cardiovascular systems.⁽²⁾

There are four different receptors that these naturally produced relaxin proteins are considered to be binding agents with, namely RXFP-1, RXFP-2, RXFP-3 and RXFP-4. Each receptor has a different action, as outlined below:⁽²⁾

• RXFP-1 receptor is suggested to influence sperm motility
• RXFP-2 receptor appears to impact testicular development
• RXFP-3 receptor may play a role in circadian rhythm and sleep cycle regulation
• RXFP-4 receptor has shown signs of affecting hunger hormone signaling cycles

Due to the variety of receptors involved and such a wide range of biological impact, extensive research has been conducted on the relaxin protein and its analogues, such as B7-33 peptide, to fully understand their potential.

Overview

B7-33 is a singular chain peptide, a smaller analogous derivative of the endogenous relaxin protein.⁽³⁾ Typically, the relaxin peptide is composed of four components - a signal peptide, B chain, C chain, and COOH terminal. Several studies were conducted initially to replicate these peptide structures, however the researchers reported that results indicated it being highly insoluble and inactive. After extensive subsequent research, scientists modified the structure by producing B chain and elongating the COOH terminal, thereby forming the first ever soluble analogue - B7-33 peptide - in 2016.⁽³⁾

Besides the structural difference, the peptide has some other variations from the endogenous proteins. B7-33 peptide has been suggested to act via pERK pathway instead of the cAMP pathway. H2-relaxin has been suggested to produce antifibrotic potential via cAMP pathway, which may potentially stimulate the formation of tumors.⁽¹⁾ Furthermore, the peptide may have a strong affinity towards the RXFP-1 receptors. The peptide appears to bind with these RXFP-1 receptors, stimulating pERK pathway, which then may lead to increased synthesis of MMP-2 matrix metalloproteinase chemicals. These chemicals then possibly inhibit the scarring of tissues, thereby preventing fibrosis.⁽¹⁾

Research and Clinical Studies

B7-33 Peptide and Vasoprotection

This 2017 study⁽⁴⁾ was conducted on male wistar rats where their tails were presented a placebo (which was sodium acetate), H2 relaxin, or B7-33 peptide. After three hours, these mice were examined for their vascular functions, mainly in the mesenteric artery, renal artery and their abdominal aorta. While the results were not as promising in the renal artery and abdominal aorta, both B7-33 and H2 relaxin were reported to exhibit improved vasodilatory properties in the mesenteric artery.

To understand better, an additional study⁽⁴⁾ was carried out in female mice who were experimentally induced with endothelial dysfunction. These mice were then either given B7-33 or H2 relaxin. Following the study, it was suggested by the researchers that both the compounds may have helped combat and prevent further spread of endothelial dysfunction in mice. These results suggest that B7-33 has the potential to replicate the vasoprotective action of H2 relaxin and thereby protect blood vessels from further damage.

B7-33 Peptide and Preeclampsia

Preeclampsia is a pregnancy ailment characterized by increased hypertension in mothers and decreased fetal weight. This clinical study⁽⁵⁾ was conducted to understand the potential of B7-33 peptide in pregnant females with preeclampsia. A cell culture of cytotrophoblasts (CTBs) was used. Cytotrophoblasts are the cells found in the inner cellular layer of the embryo. These cells were given either placebo, or marinobufagenin steroid or glucose for 2 days. Following this preparation, some of these cells were then given either a relaxin antagonist, or the B7-33 compound. Upon examination, it seemed that the cells given B7-33 peptide appeared to exhibit an upregulation of the vascular endothelial growth factor, VEGF. Cells that were given relaxin antagonists exhibited apparent reduced VEGF concentration.

B7-33 Peptide and Anti-Fibrosis

Studies⁽⁶⁾⁽⁷⁾ have suggested that when presented with a fully-extended strain of H2 relaxin protein, it may induce an increased heart rate and possibly stimulate the spread of carcinogenic cells. This is mainly attributed to its mechanism as it activates cAMP pathway. Hence, researchers are looking for a derivative that might produce the exact biological action of anti-fibrosis without cAMP activation. When the peptide was given to mice with myocardial infarction, it was reported to result in almost 50% reduction in cardiac tissue fibrosis.

Furthermore, a study⁽¹⁾ was also conducted in mice with prostate diseases. These mice were presented with two different concentrations of B7-33 peptide. At both the concentrations the results were the same, and researchers suggested that the compound might contribute to the development of fibrosis without promoting the spread of prostate tumors. This suggested that the peptide has the potential to act via the pERK pathway and not via cAMP activation.

B7-33 Peptide and Coating Material

In one animal study,⁽⁸⁾ a device was implanted in experimental mice, which was coated with the peptide. The researchers were curious to see if the peptide might counteract possible fibrotic actions in the mice. As a result of this peptide release from the device coating, the reduction in device thickness (by fibrosis) was reported to be decreased by 49.2% over the 6 week duration of study.

B7-33 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

References:

1. Mohammed Akhter Hossain et al, A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1, Drug Discovery Biology Pharmacology Monash Biomedicine Discovery Institute, Vol 7, 2016. https://research.monash.edu/en/publications/a-single-chain-derivative-of-the-relaxin-hormone-is-a-functionall
2. R J Summers, Recent progress in the understanding of relaxin family peptides and their receptors, British Journal of Pharmacology, Vol 174, issue 10, pg 915-920. https://doi.org/10.1111/bph.13778
3. Nitin A Patil et al, Relaxin family peptides: structure–activity relationship studies, British Pharmacological Society, vol 174 issue 10, published 06 December 2016. https://doi.org/10.1111/bph.13684
4. Marshall SA, O'Sullivan K, Ng HH, Bathgate RAD, Parry LJ, Hossain MA, Leo CH. B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). Eur J Pharmacol. 2017 Jul 15;807:190-197. doi: 10.1016/j.ejphar.2017.05.005. Epub 2017 May 3. PMID: 28478069. https://pubmed.ncbi.nlm.nih.gov/28478069/
5. S.H Afroze et al, Abstract P3042: Novel Peptide B7-33 and It's Lipidated Derivative Protect Cytotrophoblasts From Preeclampsia Phenotype in a Cellular Model of the Syndrome, 4 Sep 2019. https://doi.org/10.1161/hyp.74.suppl_1.P3042
6. Silvertown JD, Ng J, Sato T, Summerlee AJ, Medin JA. H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer. 2006 Jan 1;118(1):62-73. https://pubmed.ncbi.nlm.nih.gov/16049981
7. Shu Feng, Irina U. Agoulnik, Natalia V. Bogatcheva, Aparna A. Kamat, Bernard Kwabi-Addo, Rile Li, Gustavo Ayala, Michael M. Ittmann and Alexander I. Agoulnik, Relaxin Promotes Prostate Cancer Progression, March 2007. https://clincancerres.aacrjournals.org/content/13/6/1695
8. N.Welch et al, Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation, ACS Applied Materials and Interfaces, Nov 2019. https://www.researchgate.net/publication/337205944_Coatings_Releasing_the_Relaxin_Peptide_Analogue_B7-33_Reduce_Fibrotic_Encapsulation