TB-500

Overview

TB-500 is the designation used for synthetic thymosin beta-4, a 43-residue peptide that is the principal actin-sequestering molecule in mammalian cells. It is studied in research on cell migration, wound repair, angiogenesis and inflammation.

Its biology is unusually well established compared with most compounds in this catalogue — thymosin beta-4 is a genuine endogenous protein with a defined and non-controversial primary function. What is less settled is how that primary function relates to the tissue-repair effects the compound is studied for.

A note on the name, and how to check what you have

“TB-500” and “thymosin beta-4” are used interchangeably in most supplier material, but historically they are not the same thing. The TB-500 designation originally referred to a short fragment containing the actin-binding motif — seven residues, around 889 g/mol — rather than the complete peptide.

In practice, almost everything sold as TB-500 today is full-length thymosin beta-4, and there is a simple way to confirm which one you are looking at: check the molecular weight. Full-length thymosin beta-4 is approximately 4,963 g/mol. The short fragment is under 900. There is no ambiguity between those two figures.

The material described on this page is the full-length 43-residue peptide, at 4,963 g/mol.

Chemical identity

• Also known as: Thymosin beta-4, Tβ4
• Sequence: Ac-Ser-Asp-Lys-Pro-Asp-Met-Ala-Glu-Ile-Glu-Lys-Phe-Asp-Lys-Ser-Lys-Leu-Lys-Lys-Thr-Glu-Thr-Gln-Glu-Lys-Asn-Pro-Leu-Pro-Ser-Lys-Glu-Thr-Ile-Glu-Gln-Glu-Lys-Gln-Ala-Gly-Glu-Ser
• CAS number: 77591-33-4
• Molecular formula: C₂₁₂H₃₅₀N₅₆O₇₈S
• Molecular weight: 4963.0 g/mol
• Classification: Actin-sequestering peptide
• Length: 43 residues, N-terminally acetylated

Two compositional points matter later. Eleven of the forty-three residues are aspartate or glutamate, making this a strongly acidic and highly water-soluble peptide. And the single sulfur atom in the formula is one methionine at position 6 — there is no cysteine, so no disulphide to maintain.

What thymosin beta-4 actually does

The established function is straightforward and has nothing directly to do with healing.

Actin exists in cells in two forms: free monomers (G-actin) and polymerised filaments (F-actin). The balance between them governs cell shape, movement and division, and it has to be controlled tightly — uncontrolled polymerisation would turn the cytoplasm into a gel.

Thymosin beta-4 is the main protein that holds that balance. It binds G-actin monomers one-to-one and keeps them out of filaments, maintaining a reservoir of unpolymerised actin the cell can draw on. It is abundant — among the more plentiful proteins in many cell types — precisely because that reservoir needs to be large.

When a cell needs to move, it builds filaments at its leading edge from that reservoir. So the peptide’s role in cell migration follows directly from its role as an actin buffer, and cell migration is what tissue repair largely consists of.

The actin-binding motif

Binding is mediated by a short internal sequence, LKKTETQ, at residues 17–23. That heptapeptide is the functional core, and it is what the original TB-500 designation referred to.

Whether the fragment reproduces the full peptide’s activity is a real question rather than a settled one. It carries the actin-binding motif, but the full-length peptide is an intrinsically disordered protein whose activity may depend on regions outside that motif, and the two are not automatically interchangeable. Papers reporting on one are not straightforwardly evidence for the other — worth checking which was administered when reading the literature.

Beyond actin

The reported effects on tissue repair, angiogenesis and inflammation are not obviously explained by actin sequestration alone, and this is the compound’s open question.

Published work has described associations with integrin-linked kinase signalling, with vascular endothelial growth factor, with matrix metalloproteinase expression, and with anti-inflammatory activity in injury models. A well-known line of research examined effects on cardiac cell migration and survival following injury.

The field’s own term for this is “moonlighting” — a protein with a defined housekeeping role turning out to have additional signalling functions. That framing is honest about the state of understanding: the additional functions are reported and reproducible, and how they connect to the actin role is not fully worked out.

Areas of research investigation

Wound and soft tissue repair

The largest body of work, covering dermal wound models and connective tissue injury.

Cardiac injury

A distinct line examining cardiomyocyte survival and migration after ischaemic injury, which attracted attention beyond the immediate field.

Corneal and epithelial repair

Work in ocular surface models, where thymosin beta-4 progressed further toward formal investigation than in most other indications.

Why it is paired with BPC-157

Three products in this catalogue combine TB-500 with BPC-157, and the pairing has a rationale worth stating.

The two compounds are studied for overlapping outcomes through non-overlapping mechanisms. BPC-157’s reported effects centre on angiogenesis and growth factor signalling, without an identified receptor. Thymosin beta-4 acts through a defined and abundant intracellular protein interaction affecting cell motility. One works, as far as anyone can tell, on signalling; the other on the cytoskeletal machinery that responds to it.

That is the reasoning behind combining them. It is a mechanistic argument rather than an empirical one — controlled comparisons of the combination against either alone are not well represented in the literature, so the pairing is better described as plausible than as demonstrated.

Handling, reconstitution and storage

• Highly water-soluble. Eleven acidic residues make this one of the easier peptides here to get into solution.
• Methionine oxidation is the main chemical degradation route. One methionine, no cysteine and no tryptophan means a single well-defined vulnerability rather than several.
• Lyophilised storage: sealed, refrigerated, protected from light; freeze for long-term storage.
• Reconstitution: add diluent slowly down the vial wall, allow to dissolve undisturbed, do not shake. At 43 residues this is a long, disordered chain and mechanically fragile.
• After reconstitution: refrigerate and minimise freeze–thaw cycles.
• Concentration: our peptide reconstitution calculator converts vial quantity, diluent volume and syringe size into concentration per unit.

Purity and analytical verification

At 43 residues this is the longest peptide in this catalogue, and length is itself the analytical problem. Each coupling step in solid-phase synthesis proceeds at slightly less than perfect efficiency; over forty-three steps those shortfalls compound, so crude material contains a substantial population of deletion sequences — peptides missing one or two residues somewhere along the chain. They are chemically similar to the target and closely spaced chromatographically. A high purity figure for a peptide this long represents considerably more purification work than the same figure on a hexapeptide.

There is a second question specific to this molecule. Native thymosin beta-4 is acetylated at its N-terminus, and that acetylation is part of the natural structure rather than a stabilising modification added by a manufacturer. A synthesis that omits it produces a peptide 42 Da lighter — the mass of the acetyl group.

That is a clean check. The stated mass of 4,963 g/mol corresponds to the acetylated form; material reported near 4,921 is the non-acetylated variant, which is a different molecule from the native peptide. Mass spectrometry distinguishes the two easily, so the mass figure on a certificate is directly meaningful here.

We publish third-party certificates of analysis by batch.

References

• Goldstein AL, Hannappel E, Kleinman HK. Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. Trends in Molecular Medicine, 2005. PMID 16099219
• Bock-Marquette I, Saxena A, White MD, et al. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature, 2004. PMID 15565145
• Malinda KM, Sidhu GS, Mani H, et al. Thymosin beta4 accelerates wound healing. Journal of Investigative Dermatology, 1999. PMID 10469335

Summary

TB-500 is synthetic thymosin beta-4, CAS 77591-33-4, molecular formula C₂₁₂H₃₅₀N₅₆O₇₈S, molecular weight 4,963.0 g/mol — a 43-residue, N-terminally acetylated peptide and the principal actin-sequestering protein in mammalian cells. Its established function is to bind G-actin monomers and maintain the unpolymerised reservoir cells draw on when they move, which connects it directly to cell migration and therefore to tissue repair. Reported effects on angiogenesis, inflammation and cardiac injury go beyond what actin sequestration alone explains, and the field describes it as a moonlighting protein for that reason. The name is worth checking against molecular weight: at 4,963 g/mol this is the full-length peptide, not the seven-residue fragment the TB-500 designation originally described.

For laboratory research use only. Not for human consumption. This material is not a drug, food, or cosmetic and may not be sold or used for any purpose other than in vitro or non-human laboratory research.