Single-chain peptide B7-33 is a synthetic analog of the naturally occurring protein H2-relaxin. The relaxin-like anti-fibrotic potential of this peptide has been reported to be maintained without any increase in cAMP production. Research on B7-33 suggests that it may stimulate the activation of ERK1/2 and the production of matrix metalloproteinase 2 (MMP2), which might result in the degradation of extracellular collagen. [i]
Peptide B7-33
The four standard parts of the relaxin peptide are the signal peptide, B chain, C chain, and COOH terminal. Many attempts were made to duplicate these peptide structures; however, it was claimed that the copies were both insoluble and ineffective. In 2016, after years of study, scientists created the first apparently soluble analog, B7-33 peptide, by modifying the structure by creating a B chain and elongating the COOH terminus. [ii]
Activation of the p38/ERK/MAPK Pathway and B7-33
Data suggests that the B7-33 peptide, rather than the cAMP pathway often linked to the purported anti-fibrotic actions of H2-relaxin, may activate the pERK pathway.
H2-relaxin's presence has been suggested to have major effects, including the stimulation of tumor development via the activation of the cAMP pathway. Furthermore, the B7-33 peptide may have a high affinity for the RXFP-1 receptors [iii]. Increased production of MMP-2 matrix metalloproteinase may arise from the peptide's binding to these receptors, which might trigger activation of the PERK pathway. Scientists regard these enzymes as protective against the development of fibrosis because of their potential to reduce scarring of damaged tissues. [iii]
Vasoprotection and B7-33 Peptide
H2 relaxin has been studied within the context of heart failure and fibrosis due to its potential as a vasoprotective agent. The difficulty and high cost of exogenous manufacture of H2 relaxin have prompted research on its analog B7-33 peptide.
Male Wistar rats were used in research investigations, given either a placebo, H2 relaxin or B7-33 peptide to their tails. After three hours, the mesenteric artery, the renal artery, and the abdominal aorta were examined for vascular function. Findings suggest that B7-33 and H2 relaxin appeared to have increased vasodilatory qualities in the mesenteric artery, although they have little effect on the renal artery and abdominal aorta.
In addition, another investigation was performed with B7-33 or H2 relaxin in female mice with experimentally induced endothelial dysfunction. The results suggest that both compounds appeared to help reduce endothelial dysfunction's severity and helped keep it from spreading.
In conclusion, as stated by Sarah A. Marshall et al., "equimolar quantities of B7-33 duplicated the acute favorable vascular effects of serelaxin in rat mesenteric arteries and also reversed endothelial dysfunction caused by fetal trophoblast conditioned media in mouse mesenteric arteries." Researchers propose that B7-33 deserves attention as a vasoactive agent in research on cardiovascular disorders. [iv]
Preeclampsia and B7-33 Peptide
Preeclampsia is a potentially fatal pregnancy condition marked by maternal hypertension and fetal growth restriction. One scientific investigation was performed utilizing the cell culture of cytotrophoblasts (CTBs), cells located in the inner cellular layer of the embryo, to investigate the possible effect of the B7-33 peptide on preeclampsia.
For 2 days, CTBs were given either a placebo, the steroid marinobufagenin (MBG), or glucose. The B7-33 chemical was presented to all cells in the experiment, and a relaxin antagonist was given to part of the cells after that.
The findings of this study suggested that the B7-33 peptide may potentially boost VEGF levels in all cells. Notably, the VEGF levels in the cells seemed to have been reduced, as suggested by the relaxin antagonist. These results suggest the B7-33 peptide might reduce blood sugar and marinobufagenin levels that are too high. [v]
Inhibition of Fibrosis and B7-33 Peptide
The stimulation of cAMP has been hypothesized as a mode of action for H2 relaxin, which some research suggests may promote the spread of cancerous cells. To create a derivative that might display the putative anti-fibrosis function of H2 relaxin without stimulating cAMP, researchers developed the B7-33 peptide.
B7-33 peptide presentation in rats with myocardial infarction appeared to have resulted in less cardiac tissue fibrosis and enhanced heart function, which suggests fewer long-term consequences. Matrix metalloproteinase protein is thought to inhibit collagen-damaging cells and prevent fibrosis; the peptide's propensity to enhance its concentration may account for this. [vi] [vii]
Conclusion
Studies suggest the B7-33 peptide is a structural variant of the H2 relaxin protein at the COOH terminus. The peptide has been hypothesized to have more potential than H2 relaxin because of its ability to activate the pERK pathway without triggering cAMP activation, which might promote the growth of cancer cells.
Research suggests potential cardiovascular and pulmonary dysfunction properties have been linked to B7-33's anti-fibrotic activity and vasoprotective characteristics.
Please be aware that these items are designed only for use in scientific study. This peptide is not for human consumption. Please read our Terms & Conditions and comply with them before placing an order. B7-33 is available at Core Peptides for licensed professionals interested in further studying the potential of this compound
References
[i] Summers RJ. Recent progress in the understanding of relaxin family peptides and their receptors. Br J Pharmacol. 2017 May;174(10):915-920. doi: 10.1111/bph.13778. PMID: 28447360.
[ii] Nitin A Patil et al, Relaxin family peptides: structure–activity relationship studies, British Pharmacological Society, vol 174 issue 10, published 06 December 2016.
[iii] 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.
[iv] 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.
[v] S.H Afroze et al., Abstract P3042: Novel Peptide B7-33 and Its Lipidated Derivative Protect Cytotrophoblasts From Preeclampsia Phenotype in a Cellular Model of the Syndrome, 4 Sep 2019.
[vi] 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.
[vii] 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.
