B7-33

H2-relaxin is a naturally occurring, endogenous protein compound, which was synthetically mimicked and named the “B7-33” peptide. The H2-relaxin protein class comprises 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. Considered structurally similar to H2-relaxin, the synthetic equivalent B7-33 may possess anti-fibrotic potential.

B7-33

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

• 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 indications of affecting hunger hormone signaling cycles

Due to the variety of receptors involved and a wide range of biological impact, extensive research has been conducted on the relaxin protein and its analogs, such as the 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. Typically, the relaxin peptide comprises 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 a B chain and elongating the COOH terminal, thereby forming the first-ever soluble analog – B7-33 peptide – in 2016.

Besides the structural difference, the peptide has other variations from the endogenous protein. B7-33 peptide has been suggested to act via the pERK pathway instead of the cAMP pathway. The pERK pathway is a signaling route within cells that may affect cell function, often related to cell growth and survival. In contrast, the cAMP pathway involves different cellular activities primarily related to energy balance and metabolism. H2-relaxin has been suggested to produce antifibrotic potential via the cAMP pathway, which may stimulate tumor formation. Furthermore, the peptide may have a strong affinity towards the RXFP-1 receptors.

The peptide appears to bind with these RXFP-1 receptors, stimulating the pERK pathway, which then may lead to increased synthesis of MMP-2 matrix metalloproteinase chemicals. MMP-2 is an enzyme that breaks down proteins and plays a crucial role in tissue remodeling and repair. These chemicals then possibly inhibit the scarring of tissues, thereby preventing fibrosis. Fibrosis is considered the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process, which is associated with a loss of function.