B7-33 Peptide: A Streamlined Relaxin Analog with Far-Reaching Research Potential

The B7-33 peptide emerges as a uniquely structured peptidic analog that may redefine explorations into fibrosis, vascular modulation, and molecular scaffolding. Originating from the B-chain of H2-relaxin, this simplified, single-chain derivative might offer research domains a more accessible and tunable reagent. Its solubility enhancements, receptor selectivity, and signaling bias suggest it might potentially serve as a versatile tool across diverse investigative disciplines.

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Structural Composition and Receptor Engagement

B7-33 is crafted from amino acids 7–29 of the B-chain of H2-relaxin, augmented with a KRSL tail to markedly boost solubility compared to earlier truncated forms. This streamlined design is believed to enable more efficient synthesis—rendering it more practical for prolonged research use.

Critically, the peptide seems to interact selectively with the relaxin family peptide receptor 1 (RXFP1) and may preferentially initiate signaling via the ERK1/2 (pERK) pathway rather than the cAMP route commonly activated by full-length H2-relaxin. This biased signaling characteristic may allow researchers to dissect downstream molecular processes with greater precision.

Antifibrotic Property and Extracellular Remodeling Research

One of the compelling attributes of B7-33 is its apparent antifibrotic properties. Investigations indicate that the peptide may engage RXFP1-AT2 receptor heterodimers, possibly initiating pERK-mediated upregulation of matrix metalloproteinase-2 (MMP-2), which might ostensibly facilitate extracellular collagen turnover and mitigate fibrotic deposition.

Moreover, researchers have posited that coatings incorporating B7-33, such as PLGA-based controlled-release platforms, might reduce fibrotic encapsulation over longer durations in research materials, potentially serving as an innovative interface in tissue-engineering and device coating domains.

Vascular and Vasoprotective Research Implications

B7-33 is inferred to retain significant vascular modulation properties of H2-relaxin but with a more targeted profile. Studies suggest that the peptide might promote vasodilatory modulation via RXFP1 engagement—possibly involving nitric oxide (NO) pathways or endothelium-derived hyperpolarizing factor mechanisms—though it is not believed to fully replicate cAMP-driven vasodilatory cascades.

Specifically, research models suggest that B7-33 may support vasodilation in mesenteric vascular systems—mirroring the vascular outcomes of serelaxin analogs—without the need for extensive receptor promiscuity. This potential property may render it plausible for further examination in vascular tone regulation, endothelial responsiveness, and mechanistic pathways modulating systemic or localized vascular resistance in experimental settings.

Cardioprotective and Remodeling Modulation Research

Within models of ischemia-reperfusion and myocardial insult, B7-33 appears to preserve the contractile integrity of cardiac tissue under stress. Investigations indicate that the peptide may limit infarct-like remodeling by decreasing endoplasmic reticulum stress markers (e.g., GRP78) and preserving fractional shortening metrics in research parameters, suggestive of a cardioprotective influence.

These findings could make B7-33 a promising investigational reagent in exploring the molecular underpinnings of myocardial resilience, repair mechanisms, and stress-induced remodeling without the complexity of full-length peptide analogs.

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Molecular Engineering and Scaffold Optimization

Research efforts have been directed toward generating a minimal active scaffold based on B7-33. Substitutions, truncations, and structural modifications (e.g., alanine scanning, hydrocarbon stapling, Aib incorporation) have been explored to refine binding affinity to RXFP1 domains, especially within engineered constructs like 7BP. It is theorized that key residues such as R^B13, R^B17, and I^B20 are central to binding, and that maintaining structural flexibility may be critical for activation—highlighting the peptide's potential as a modular design template.

This tunability positions B7-33 as a potential starting point for developing analogs with tailored receptor affinity, signaling bias, or half-life properties—all of which are valuable for biochemical tool development and receptor pharmacology investigations.

Emerging Research Domains and Speculative Applications

Beyond fibrosis and vascular modulation, B7-33 might be of speculative interest in regenerative biology, tissue engineering, and cellular resilience studies. By possibly promoting extracellular matrix turnover and modulating repair pathways, the peptide may potentially be integrated into scaffolds or biomaterial systems to interrogate interactions between cellular populations and remodeling environments.

Moreover, the peptide's receptor specificity and signaling bias may allow exploration into inflammatory or stress response pathways—investigations into how RXFP1-mediated ERK activation may intersect with inflammatory or anti-hypertrophic signaling circuits could be particularly revealing.

Summary and Outlook

The B7-33 peptide may represent a compact, tunable, and functionally selective analog of H2-relaxin, offering research communities a streamlined reagent with intriguing properties, including:

1. Enhanced solubility and synthesis feasibility

2. RXFP1-selective bias toward pERK signaling rather than cAMP

3. Putative antifibrotic remodeling through MMP-2 modulation

4. Vasoprotective potential via non-cAMP pathways such as NO or EDH

5. Preservation of contractile function under ischemic-like stress in models

6. Amenability to structural refinement for receptor engagement studies

7. Applicability in biomaterial coatings to attenuate fibrotic encapsulation

By avoiding complexities linked to full-length relaxin, B7-33 seems to offer cleaner, mechanistic insights and may catalyze novel experimental frameworks in cardiovascular, fibrotic, and tissue-regenerative research contexts. Its modular nature and signaling precision position it as a versatile scaffold, perhaps serving as a linchpin in future explorations into GPCR biased agonism and extracellular remodeling dynamics. Researchers interested in further investigating the potential of this peptide are encouraged to visit this website for the best research materials and the most accurate peptide data available online. 

References

[i] Stremming, J.W., Lok, M.C., Sundgren, N.C., White, F.M., & Duan, C. (2022). Human recombinant long arginine-3 IGF-1 (LR3 IGF-1) promotes organ-specific growth and myoblast proliferation in the fetal sheep. Frontiers in Physiology, 13, Article 954948. https://doi.org/10.3389/fphys.2022.954948.

[ii] Hossain, M.A., Handley, T., Tailhades, J., Praveen, P., & Akhter, M. (2023). Further developments towards a minimal potent derivative of human relaxin-2. International Journal of Molecular Sciences, 24(16), Article xxxx. https://doi.org/10.3390/ijms241612646.

[iii] Marshall, A.J., Tailhades, J., Handley, T., et al. (2016). B7-33, a functionally selective relaxin receptor 1 agonist, confers acute cardioprotection and limits myocardial infarction–related adverse remodeling in mice by attenuating cardiomyocyte death and endoplasmic reticulum stress. Journal of the American Heart Association, 5(e015748). https://doi.org/10.1161/JAHA.119.015748.

[iv] Hossain, M.A., Marshall, A.J., et al. (2017). B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin): anti-fibrotic, vasodilatory, and anti-inflammatory effects. International Journal of Molecular Sciences, 18(?–?)

[v] Stremming, J. A., Brown, L., & Rozance, P. J. (Year). Effects of LR3 IGF-1 infusion on organ-specific growth and skeletal muscle myoblast proliferation in late-gestation fetal sheep. Frontiers in Physiology, Article ID, Volume(Issue).

By ML Staff. Images courtesy of DepositPhotos