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TB-500 vs thymosin beta-4: fragment and parent

TB-500 is the seven-residue synthetic peptide Ac-LKKTETQ, and its sequence is taken from positions 17 to 23 of thymosin beta-4, a 43-residue protein.[1],[2],[3]

The doping-control laboratories that identified TB-500 describe the relationship in exactly those terms, as the N-terminally acetylated 17-23 fragment of the parent.[3],[4]

What follows sets out each molecule's recorded identity and the actin-binding segment they share, and it carries no finding from one molecule across to the other.

Identity side by side

AttributeTB-500Thymosin beta-4
Registry description[1],[2]N-terminal acetylated 17-23 fragment of thymosin beta 4Thymosin β-4 (human)
FDA UNII[1],[2]QHK6Z47GTG549LM7U24W
CAS Registry Number[5],[6],[2]885340-08-977642-24-1
Length[1],[2]7 residues43 residues
Sequence[5],[2]Ac-Leu-Lys-Lys-Thr-Glu-Thr-GlnSDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES (one-letter)
N-terminus (registry)[1],[2]Acetylated leucineN-acetyl-serine annotated at position 1
Molecular formula[5],[7]C38H68N10O14Not stated on this page
Target or activity recorded[5],[7]Actin (the parent's actin-binding site, residues 17 to 23)No molecular target recorded; classified as an actin-binding peptide

Where does TB-500 sit within thymosin beta-4?

Counting from the N-terminus of the registry's 43-residue sequence, residues 17 to 23 read LKKTETQ, the same seven residues that make up TB-500.[2],[1]

The fragment departs from that stretch of the parent by an acetyl group on its N-terminal leucine, which the equine doping-control paper calls artificial acetylation.[4]

With thirty-six residues fewer than the parent, the fragment has its own formula, mass and CAS number.[1],[2],[5]

What pathway link does the literature record?

The 2003 motif study describes thymosin beta-4 as a ubiquitous 5 kDa polypeptide regarded as the main G-actin-sequestering peptide in mammalian tissue.[8]

Analytical work on TB-500 identifies positions 17 to 23 as the part of thymosin beta-4 responsible for binding actin.[4]

That 2003 study tested a synthetic seven-amino-acid actin-binding motif, but its abstract does not say whether the peptide was acetylated, so none of its results is attributed to TB-500 here.[8]

Metabolism work on TB-500 names shorter acetylated pieces among its breakdown products, with Ac-LK the most abundant early metabolite in rats and Ac-LKK detected for up to 72 hours.[9]

What does the literature not establish?

None of the publications cited here tested TB-500, confirmed as the acetylated fragment, alongside full-length thymosin beta-4 in one experiment.[3],[4],[8],[9]

Published trials of full-length thymosin beta-4 used the 43-residue peptide; they are recorded on that compound's page and are not evidence about the fragment.[10],[11]

One metabolite study goes further and suggests that activity attributed to TB-500 may belong to its breakdown product Ac-LKKTE rather than to the seven-residue parent.[9]

Limitations

Sharing seven residues with a larger protein does not give a fragment that protein's properties, and nothing here assumes it does.[5]

Most published work on this exact fragment is analytical detection and metabolism, not biology.[3],[4],[9]

Compound profiles

References

  1. U.S. FDA Global Substance Registration System (GSRS), TB-500, UNII QHK6Z47GTG. UNII QHK6Z47GTG · CAS 885340-08-9
  2. U.S. FDA Global Substance Registration System (GSRS), Thymosin β-4, UNII 549LM7U24W. UNII 549LM7U24W · CAS 77642-24-1
  3. Esposito S, Deventer K, Goeman J, et al. Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Drug Test Anal. 2012;4(9):733-738. PMID 22962027 · DOI 10.1002/dta.1402
  4. Ho EN, Kwok WH, Lau MY, et al. Doping control analysis of TB-500, a synthetic version of an active region of thymosin β4, in equine urine and plasma by liquid chromatography-mass spectrometry. J Chromatogr A. 2012;1265:57-69. PMID 23084823 · DOI 10.1016/j.chroma.2012.09.043
  5. TB-500 research profile, PepGenex Science (identity and records, with their sources).
  6. U.S. National Library of Medicine, ChemIDplus record for Thymosin beta-4, as deposited in PubChem (Substance SID 381122663). PubChem SID 381122663 · CAS 77642-24-1 · UNII 549LM7U24W
  7. Thymosin beta-4 research profile, PepGenex Science (identity and records, with their sources).
  8. Philp D, Huff T, Gho YS, et al. The actin binding site on thymosin beta4 promotes angiogenesis. FASEB J. 2003;17(14):2103-2105. PMID 14500546 · DOI 10.1096/fj.03-0121fje
  9. Rahaman KA, Muresan AR, Min H, et al. J Chromatogr B Analyt Technol Biomed Life Sci. 2024;1235:124033. PMID 38382158 · DOI 10.1016/j.jchromb.2024.124033
  10. Ruff D, Crockford D, Girardi G, Zhang Y. Title withheld on this site (see the publication record). Annals of the New York Academy of Sciences 2010. PMID 20536472 · DOI 10.1111/j.1749-6632.2010.05474.x
  11. Guarnera G, De Rosa A, Camerini R. Thymosin beta-4 and venous ulcers: clinical remarks on a European prospective, randomized study on safety, tolerability, and enhancement on healing. Annals of the New York Academy of Sciences 2007. PMID 17495250 · DOI 10.1196/annals.1415.003