What Is B7-33? A Single-Chain Relaxin Mimetic

Cover illustration: AI-generated editorial artwork. Conceptual only; not an exact molecular structure, actual laboratory result or evidence of clinical effects.

B7-33 is a protein-engineering answer to a manufacturing problem. Native human relaxin-2 is a two-chain peptide hormone held together by disulfide bonds — insulin-like in architecture, and like insulin, awkward and expensive to produce. B7-33 is an attempt to recover part of its activity using a single 27-residue chain that solid-phase synthesis can make routinely. Whether that works, and in what sense, is what the literature addresses.

For laboratory research use only. The research materials supplied by HealthyWelness are not approved medicines, foods or cosmetics and are not for human or veterinary use. This article summarises published research and is not medical advice.

The molecule

Property	Value
Origin	Residues 7–33 of the human relaxin-2 B chain
Length	27 residues
Architecture	Single chain
Native comparator	Relaxin-2 — two chains, disulfide-linked
Receptor	RXFP1
Signalling description	Functionally selective, per published work
Synthesis route	Standard solid-phase peptide synthesis

The naming convention is worth decoding, because it is informative rather than arbitrary: B for the B chain, 7–33 for the residue range retained. The peptide is a fragment, not an analogue with substitutions, which means it can be compared directly against the corresponding region of the native hormone.

Dropping the A chain removes the interchain disulfides entirely. That is the whole point of the design, and it changes the handling profile completely: a single-chain linear peptide does not scramble its disulfides, does not need reducing-agent-free buffers for that reason, and is made by the same chemistry as any other 27-mer.

What “functionally selective” means in this literature

The term appears in the title of the 2020 paper by Devarakonda and colleagues in the Journal of the American Heart Association, and it is easy to misread. It does not mean selective for one receptor subtype over another. It means that engagement of RXFP1 by B7-33 is reported to favour some downstream signalling arms over others, relative to the native hormone.

Signalling bias of this kind is a real and well-recognised phenomenon at G protein-coupled receptors, and it has a specific experimental consequence: an agonist described as biased cannot be assumed to reproduce the native ligand’s effects across readouts. Matching one downstream measure does not predict the next. Experiments that compare B7-33 with relaxin therefore need to specify which arm of signalling is being measured, and a divergence between them is a finding rather than an inconsistency.

The published work, by model

Study	Year	Model	Comparator
Marshall, Eur J Pharmacol	2017	Vascular function	Serelaxin (recombinant relaxin-2)
Praveen, Mol Cell Endocrinol	2019	Receptor pharmacology, single-chain agonists	Other single-chain designs
Welch, ACS Appl Mater Interfaces	2019	Implant coating, fibrotic encapsulation	Uncoated material
Devarakonda, J Am Heart Assoc	2020	Mouse myocardial infarction, cardiac remodelling	Vehicle
Alam, Biomed Pharmacother	2023	Experimental cardiomyopathy, ventricular fibrosis	Perindopril

Two things stand out from this table. First, the literature is comparative to an unusual degree: three of the five studies measure B7-33 against something other than vehicle, including an established small-molecule drug in the 2023 study. That makes the body of work more interpretable than the typical research-peptide literature, where vehicle controls are often the only comparator.

Second, the 2019 study by Welch and colleagues is methodologically distinct from the rest. It is a materials-science paper: the peptide is released from a coating and the readout is fibrotic encapsulation of an implant. For laboratory purposes this is a valuable source, because it is one of the few places where the peptide’s behaviour in a delivery matrix — rather than in solution — is documented.

The 2019 paper by Praveen and colleagues is the one to read for design context. It covers single-chain peptide agonists of relaxin receptors as a class, which places B7-33 among its siblings rather than treating it as a one-off.

Where the literature stops

It is worth being explicit about the boundary. The published work on B7-33 is in vitro and in animal models. There is no clinical literature on this peptide, and the comparisons with serelaxin in the papers above are comparisons within experimental systems, not between therapies. Any description that elides that distinction is overstating what has been shown.

Handling

A 27-residue single-chain peptide is a moderately demanding but unexceptional reagent.

Store sealed lyophilized powder at −20 °C or below, dry and protected from light.
Reconstitute gently; swirl rather than vortex. Peptides of this length can aggregate under shear.
Expect some surface loss at low working concentrations, as with any peptide of this size. Carrier protein is used where the assay tolerates it.
Aliquot on first reconstitution and date the tubes. See storing reconstituted peptides.
Derive molarity from net peptide content, since counterion and residual water contribute to vial weight — a larger absolute correction for a 27-mer than for a short peptide. Our reconstitution calculator takes those figures.

Our B7-33 research material is supplied for laboratory research use. Certificates are available for listed products — contact us for the latest report. For a fragment peptide, confirming the observed mass against the expected value for the stated residue range is a worthwhile manual check.

Open questions

Which downstream arms of RXFP1 signalling does B7-33 favour, and which does it not engage?
How does its stability in biological matrices compare with the native two-chain hormone?
Do the comparative advantages reported against an established drug in one model hold in others?

Frequently asked questions

What is B7-33?

A single-chain peptide corresponding to residues 7 to 33 of the B chain of human relaxin-2, reported as an agonist at the relaxin family peptide receptor 1, RXFP1. It was designed to reproduce relaxin activity without the two-chain, disulfide-linked architecture of the native hormone.

Why is a single chain significant?

Native relaxin-2 is a two-chain peptide held together by disulfide bonds, which makes it expensive and difficult to produce and handle. A single chain of 27 residues can be made by standard solid-phase synthesis, which is the practical motivation for the design.

What does functionally selective mean here?

Published work describes B7-33 as biasing RXFP1 signalling towards certain downstream pathways rather than reproducing the full native signalling profile. That bias, rather than receptor subtype selectivity, is what the term refers to in this literature.

What models has B7-33 been studied in?

Rodent cardiac models predominate, including myocardial infarction and cardiomyopathy preparations, alongside vascular work and a materials study where the peptide was released from a coating. The literature is animal and in vitro, not clinical.

Is B7-33 the same as serelaxin?

No. Serelaxin is recombinant human relaxin-2, the full two-chain hormone. B7-33 is a short synthetic single-chain peptide designed to mimic part of its activity. Published work compares the two rather than treating them as equivalent.

References

Marshall SA, et al. B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). Eur J Pharmacol. 2017. PMID: 28478069 https://pubmed.ncbi.nlm.nih.gov/28478069/
Devarakonda T, et al. B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice. J Am Heart Assoc. 2020. PMID: 32295457 https://pubmed.ncbi.nlm.nih.gov/32295457/
Praveen P, et al. Single chain peptide agonists of relaxin receptors. Mol Cell Endocrinol. 2019. PMID: 30641102 https://pubmed.ncbi.nlm.nih.gov/30641102/
Welch NG, et al. Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation. ACS Appl Mater Interfaces. 2019. PMID: 31713411 https://pubmed.ncbi.nlm.nih.gov/31713411/
Alam F, et al. The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy. Biomed Pharmacother. 2023. PMID: 36753958 https://pubmed.ncbi.nlm.nih.gov/36753958/