What Are Thymic Peptides?
Thymic peptides are small peptides and proteins first identified in the search for thymus-derived factors. One group, the thymosins, came from thymosin fraction 5, a standardized extract of bovine thymus that turned out to be a mixture of small polypeptides. The main thymosins are thymosin alpha-1 and its precursor prothymosin alpha, parathymosin, and thymosin beta-4 with the other beta-thymosins. Reviews of the field conclude that none of the isolated peptides is really a thymic hormone; they are biologically important peptides with diverse functions inside and outside cells (Hannappel and Huff, 2003).
This hub explains the thymosin name, how the alpha- and beta-thymosins differ, and where thymulin and thymopoietin fit. For single compounds, see the thymosin alpha-1 overview and the TB-500 research overview.
This article is a scientific overview for laboratory researchers. The research-grade Thymosin Alpha-1 and TB-500 supplied by Prime Peptide Solutions are sold strictly for in-vitro laboratory research. They are not approved for human use and are not for human or animal consumption.
Where the Thymosin Name Comes From
Work on thymosins began in 1965, when A. White's group searched for thymic factors behind the physiological functions of the thymus (Hannappel and Huff, 2003). A 1966 paper described the preparation, assay and partial purification of a thymic lymphocytopoietic factor, which the authors called thymosin (Goldstein et al., 1966). A standardized bovine thymus extract, thymosin fraction 5, proved to be a mixture, and several of its peptides were isolated and tested: polypeptide beta-1, thymosin alpha-1, prothymosin alpha, parathymosin and thymosin beta-4 (Hannappel and Huff, 2003).
- 1977: thymosin alpha-1 was sequenced from calf thymus as a heat-stable, highly acidic peptide of 28 residues, one of several in fraction 5, and the authors suggested a nomenclature for the family of fraction 5 polypeptides (Goldstein et al., 1977).
- 1981: thymosin beta-4 was sequenced from calf thymus as a 43-residue peptide with an acetyl-blocked N-terminus and an isoelectric point of 5.1 (Low et al., 1981).
- Later: polypeptide beta-1 proved identical to ubiquitin truncated by two C-terminal glycines, and large amounts of thymosin beta-4 were found in many cells (Hannappel, 2007).
So the name records where the peptides were first found, not a shared structure. Thymosin alpha-1 and thymosin beta-4 come from different genes (PTMA and TMSB4X) and, in UniProt, belong to different protein families: the pro/parathymosin family and the thymosin beta family.
The Alpha-Thymosins
Prothymosin alpha, the precursor
Rodent tissue. Using an antibody to synthetic thymosin alpha-1, a 1984 study isolated from rat thymus a polypeptide of about 112 residues carrying the thymosin alpha-1 sequence at its N-terminus. Named prothymosin alpha, it was the major substance in rat thymus extracts that reacted with the antiserum, its isoelectric point was 3.55, and the authors concluded that it appears to be the native polypeptide from which thymosin alpha-1 and other fragments are generated during the isolation of fraction 5 (Haritos et al., 1984). UniProt lists human prothymosin alpha (gene PTMA, entry P06454) as a nuclear protein, with thymosin alpha-1 as residues 2-29.
Biophysics. Gel filtration at pH 2.8 had suggested that prothymosin alpha forms oligomers (Haritos et al., 1984). Small-angle X-ray scattering, light scattering, mass spectrometry and circular dichroism later showed it to be a monomer under physiological conditions, with a random-coil-like conformation and no regular secondary structure (Gast et al., 1995). A structural review describes all the thymosin proteins as short, highly charged and intrinsically unstructured under natural conditions, although structure can be induced in many of them by low pH, Zn2+ ions, organic solvents or binding partners (Hoch and Volk, 2016).
Parathymosin
A 1985 study isolated parathymosin alpha, about 105 residues, from rat thymus. Its first 30 residues were 43% identical to thymosin alpha-1 and prothymosin alpha, but the shared stretches do not include residues 2-9 (Haritos et al., 1985).
Thymosin Alpha-1: Molecule at a Glance
- Sequence: Ac-SDAAVDTSSE
ITTKDLKEKK EVVEEAEN-OH (28 residues) - Molecular formula: C129H215N33O55
- Molecular weight: 3108.3 g/mol
- CAS number: 62304-98-7
- PubChem: CID 16130571
- Precursor: prothymosin alpha, residues 2-29
The Beta-Thymosins
The beta-thymosins are a family of highly conserved, polar peptides of about 5 kDa that were first thought to be thymic hormones and are now known as the main intracellular G-actin-sequestering peptides, present at high concentration in almost every cell (Huff et al., 2001).
Rodent tissue. Thymosin beta-4 was found in spleen, thymus, brain, lung, liver and heart muscle of rats and mice, at high levels in peritoneal macrophages, and in tissues of athymic mice, so it does not come solely from the thymus (Hannappel et al., 1982). Thymosin beta-10 has about 75% sequence homology with thymosin beta-4 and occurs alongside it in spleen, liver, thymus and several cultured cell lines (Erickson-Viitanen et al., 1983).
Biochemistry. Fx, the actin-sequestering peptide of human platelets, has the same sequence as thymosin beta-4; the protein forms a 1:1 complex with actin monomers and inhibits their polymerization (Safer et al., 1991). Beta-thymosins act as actin buffers, holding monomers out of filaments while keeping a pool ready when the cell needs filaments (Huff et al., 2001). The complex has a micromolar dissociation constant, which allows fast binding and release; thymosin beta-4 is unstructured on its own, folds on binding G-actin, and is found in the nucleus as well as the cytoplasm (Hannappel, 2007). Oxidizing its single methionine to the sulfoxide attenuates G-actin sequestering, and the sulfoxide inhibited neutrophil chemotaxis in vitro (Young et al., 1999).
Thymosin Beta-4: Molecule at a Glance
- Sequence: Ac-SDKPDMAEIE
KFDKSKLKKT ETQEKNPLPS KETIEQEKQA GES (43 residues) - Molecular formula: C212H350N56O78S
- Molecular weight: 4963 g/mol (PubChem; the 1981 paper on the bovine protein reported 4982)
- CAS number: 77591-33-4
- PubChem: CID 16132341
- Gene: TMSB4X
Where TB-500 fits
TB-500 is not the full protein. It is the N-acetylated seven-residue peptide Ac-LKKTETQ, residues 17-23 of thymosin beta-4, a fragment that analytical work identified in TB-500 (Esposito et al., 2012). Its formula is C38H68N10O14 and its molecular weight 889.0 g/mol (CAS 885340-08-9), against 4963 for the protein. It is also one of the two peptides in Wolverine (BPC-157 + TB-500); for TB-500 against an unrelated peptide, see BPC-157 vs TB-500.
Related Thymus Peptides: Thymulin and Thymopoietin
Two other thymus peptides have separate histories and are not thymosins. Neither is sold here; they are included for context.
Thymulin
A circulating thymic factor (FTS) isolated from pig serum was sequenced as the nonapeptide pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH, and a synthetic copy showed the same biological activities (Pleau et al., 1977). FTS lost its activity in a rosette assay after metal chelation, and zinc restored it, with a 1:1 metal-to-peptide ratio giving the most activation; the authors named the zinc-containing active form thymulin (FTS-Zn) (Dardenne et al., 1982). Monoclonal antibodies later showed a zinc-specific conformation of the peptide, which is produced by thymic epithelial cells (Dardenne et al., 1985).
Thymopoietin
Thymopoietins I and II were sequenced from bovine thymus and thymopoietin III, a 49-residue polypeptide, from bovine spleen (Audhya et al., 1981). In 1979 a synthetic pentapeptide, Arg-Lys-Asp-Val-Tyr, matching residues 32-36 of thymopoietin, induced the differentiation of mouse prothymocytes to thymocytes in vitro (Goldstein et al., 1979). Cloning later found three alternatively spliced human mRNAs encoding thymopoietins alpha, beta and gamma (75, 51 and 39 kDa), whose shared N-terminal regions include sequences nearly identical to the original 49-residue protein (Harris et al., 1994). A single TMPO gene produces all three; they are nuclear proteins, and thymopoietin beta appears to be the human homologue of rat lamina-associated polypeptide 2 (LAP2) (Harris et al., 1995).
Key Studies
- Goldstein et al., 1966: partial purification of a thymic factor named thymosin. PMID 5230175
- Goldstein et al., 1977: sequence of thymosin alpha-1. PMID 265536
- Low et al., 1981: sequence of thymosin beta-4. PMID 6940133
- Haritos et al., 1984: prothymosin alpha as the native precursor. PMID 6583693
- Safer et al., 1991: thymosin beta-4 identical to the platelet actin-sequestering peptide Fx. PMID 1999398
- Hannappel and Huff, 2003: review of prothymosin alpha, parathymosin and the beta-thymosins. PMID 12852257
Handling and Storage of the Lyophilized Peptides
Thymosin Alpha-1 and TB-500 are each supplied as a lyophilized powder in a sealed 10mg vial, and Wolverine as a 20mg two-peptide vial; the product pages give the same storage: 2-8 °C, or -20 °C for long-term storage. Keep vials cold, dry and dark, and let a cold vial reach room temperature before opening so moisture does not condense on the powder. Neither thymosin alpha-1 nor TB-500 contains methionine or cysteine, so the methionine oxidation described for full-length thymosin beta-4 does not apply to them. A peptide Certificate of Analysis typically pairs HPLC purity with a mass-spectrometry identity check; the expected average masses are about 3108 for thymosin alpha-1 and 889 for TB-500. See the peptide storage guide, the lyophilization explainer and how to read a peptide COA.
Frequently Asked Research Questions
What are thymic peptides?
Peptides and proteins first identified in the search for thymus-derived factors. The thymosins came from thymosin fraction 5: the alpha-thymosins (prothymosin alpha, thymosin alpha-1, parathymosin) and the beta-thymosins such as thymosin beta-4. Thymulin and thymopoietin are separate thymus peptides.
Are thymosins thymic hormones?
Reviews conclude that none of the peptides isolated from fraction 5 is really a thymic hormone. Thymosin beta-4, for example, is found in many tissues and in athymic mice.
Is thymosin alpha-1 related to thymosin beta-4?
Only by name. They come from different genes (PTMA and TMSB4X) and different protein families.
What is prothymosin alpha?
A highly acidic nuclear protein of about 110 residues that carries thymosin alpha-1 at its N-terminus. It behaves as a monomeric random coil under physiological conditions.
What do beta-thymosins do in cells?
They bind actin monomers 1:1 and hold them out of filaments, acting as actin buffers. Thymosin beta-4 and thymosin beta-10 are two members found together in many mammalian tissues.
What are the Thymosin Alpha-1, TB-500 and Wolverine sold here intended for?
Only in-vitro laboratory research. They are not for human or animal consumption and are not equivalent to any approved medicine.
Conclusion
"Thymosin" is a historical label for peptides first pulled from thymus extracts. Prothymosin alpha, an intrinsically unstructured nuclear protein, carries thymosin alpha-1 at its N-terminus; the beta-thymosins, led by thymosin beta-4, sequester actin in almost every cell, and TB-500 is a seven-residue fragment of thymosin beta-4. Thymulin and thymopoietin are separate thymus peptides.
Disclaimer: This article is provided for educational and research purposes only. It summarizes publicly available scientific literature and does not constitute medical advice. Thymosin Alpha-1, TB-500 and all peptide compounds sold by Prime Peptide Solutions are intended strictly for laboratory research, are not approved for human use, and are not for human or animal consumption. Researchers are responsible for compliance with all applicable regulations in their jurisdiction.
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References & Further Reading
- PubMed: Thymosin literature
- PubMed: Beta-thymosins and actin
- Related: Thymosin alpha-1 overview
- Related: TB-500 research overview
Research-Grade Thymosin Alpha-1 and TB-500
In our catalog these are listed as Thymosin Alpha-1 and TB-500, each a 10mg vial of lyophilized powder. TB-500 is also in Wolverine (BPC-157 + TB-500) and in KLOW. Every batch of Wolverine (BPC-157 + TB-500) is tested by an independent third-party lab. The lab report (COA) is on our COAs page. The current Wolverine report also has its own page: Wolverine 20mg lab report.
Sold strictly for in-vitro laboratory research. Not for human or animal consumption.