TB-500 Fragment (LKKTETQ)

TB-500 Fragment (Leu-Lys-Lys-Thr-Glu-Thr-Gln; LKKTETQ; thymosin beta-4 residues 17 through 23; molecular weight 819.93) is a seven-residue synthetic peptide corresponding to the minimal actin-binding region of thymosin beta-4 (Tbeta4), the 43-residue actin-sequestering protein expressed at high concentration in platelets, leukocytes, and many other cell types. The full-length Tbeta4 sequence is the molecule supplied as Kodiac biolabs TB-500 (KDC-MN-003); the LKKTETQ fragment is a separate research-grade preparation that has been used in vendor literature and a limited research literature interchangeably with TB-500 (a confusion that should be resolved by mass spectrometry on each lot, since the fragment and full-length peptides have very different masses). The pharmacological argument for the heptapeptide is that LKKTETQ retains the cell migration and angiogenic activity of the parent at substantially lower molecular weight, with potentially favorable pharmacokinetic and tissue distribution profiles. Published in vitro and rodent studies support migration-promoting activity at this minimal sequence. The full-length Tbeta4 has additional activities (anti-inflammatory effects, regulation of cardiac and corneal repair) that depend on residues outside the 17-23 region and are not necessarily reproduced by the fragment. Investigators should specify whether the research-grade preparation in question is the full-length 43-residue peptide (KDC-MN-003) or the LKKTETQ heptapeptide (this monograph), since the published preclinical record is dominated by the full-length compound and translation of full-length results to fragment dosing should be done with caution. Reconstitution and handling parallel other small synthetic peptides; the heptapeptide is highly water-soluble and stable to lyophilization. Plasma half-life is on the order of minutes; tissue retention is shorter than for the full-length peptide.