Bioengineering & Translational Medicine · Published 2026-03-31 · DOI 10.1002/btm2.70144
Abstract Thymosin beta 4 (Tβ4) has been clinically trialed for over 10 years to treat ulcers, dry eye syndrome, and acute myocardial infarction (MI). However, as of now, no Tβ4 drug has been approved. Tβ4, as a small protein drug, has to face druggability challenges such as abundant supply, high purity, verified efficacy and safety, long half‐life, and shelf‐life. Here, a modified prokaryotic expression system was developed to express recombination Tβ4 (rTβ4), followed by single thiol‐site‐specific PEGylation of rTβ4, namely PEG‐rTβ4 as a prodrug. The identification and thermodynamic properties of PEG‐rTβ4 were tested with a matrix‐assisted laser desorption‐ionization time of flight mass spectrometer, a differential scanning calorimeter, and a thermal gravimetric analyzer. The data showed the superiority of PEG‐rTβ4 for treating MI. Long‐circulating PEG‐rTβ4 significantly relieves myocardial remodeling, restores cardiac function, promotes neoangiogenesis, and inhibits apoptosis via the Akt/Bcl‐2/caspase‐3 pathway. In summary, PEG‐rTβ4 is a better choice for the drug development of this active protein.
Abstract from DOAJ. Public domain (CC0 1.0).
Read the article at the publisher →