Work

PEGylated thymosin β4 is a thiol‐site‐specific prodrug treating myocardial infarction in vivo

Year: 2026

Type: article

Abstract: Thymosin beta 4 (Tβ 4 ) 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. Tβ 4 , 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 Tβ 4 (rTβ 4 ), followed by single thiol‐site‐specific PEGylation of rTβ 4 , namely PEG‐rTβ 4 as a prodrug. The identification and thermodynamic properties of PEG‐rTβ 4 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‐rTβ 4 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‐rTβ 4 is a better choice for the drug development of this active protein.

Source: Bioengineering & Translational Medicine

DOI: 10.1002/btm2.70144