TB-500 and Thymosin Beta-4: The Fragment Is Not the Protein

In 2012, a group at Ghent University ran commercial TB-500 through high-resolution mass spectrometry on an Orbitrap Exactive and identified its active content as Ac-LKKTETQ, the N-terminally acetylated 17-23 fragment of human thymosin beta-4. They then synthesised the same fragment by solid-phase peptide synthesis to confirm the match against an authentic standard. That paper is the reason TB-500 has a defined chemical identity at all.

The identity is precise. Molecular formula C38H68N10O14, molecular weight 889.0 g/mol, exact mass 888.4916 (PubChem CID 62707662, CAS 885340-08-9). The LKKTETQ sequence is the actin-binding motif of thymosin beta-4, the region the parent protein uses to contact monomeric actin.

Thymosin beta-4 itself is a different molecule: a 43-amino-acid protein of roughly 4,963 g/mol, described in the literature as one of the principal G-actin-sequestering molecules in eukaryotic cells. The Goldstein reviews that anchor this field, including the 2005 Trends in Molecular Medicine review, examine that full 43-residue protein across dermal and corneal contexts. They are not studies of the heptapeptide.

Product identity is a live analytical question, not a theoretical one. The Ghent group noted that TB-500 was marketed as the synthetic peptide of the active region of thymosin beta-4 with no stated amino acid sequence or molecular weight. A 2023 analysis in Drug Testing and Analysis examined products sold as TB500 and TB1000 and reported that their content was not systematically consistent with prior descriptions. Certificate of analysis, not label, is what establishes what is in a given vial.

Supplied for laboratory research use only.