Elastin-like Polypeptide Enhances the Therapeutic Activity of Thrombopoietin Mimetic Peptide

Thrombopoietin (TPO) is essential for treating thrombocytopenia, but its clinical use is limited by immunogenicity and short half-life. TMP, a TPO mimetic peptide, addresses these issues but requires fusion with carriers to improve pharmacokinetics. This study developed ELP-TMP fusion proteins (ELP120-2TMP and 2TMP-ELP120) to extend half-life and enhance activity via elastin-like polypeptide (ELP). Results showed EC50 values of 5.81 nM for ELP120-2TMP and 10.88 nM for 2TMP-ELP120, compared to 2.65 nM for recombinant human TPO (rhTPO). At a dose of 600 nmol/kg, ELP120-2TMP resulted in peak platelet counts in mice on day 20, exhibiting a half-life of 22.9 h. Conversely, 2TMP-ELP120 achieved peak platelet counts on day 12, with a half-life of 25.4 h. The half-lives of both fusion proteins were significantly longer than that reported 2TMP alone (1 h). Area under the curve (AUC) indicated superior platelet stimulation over rhTPO (p < 0.01).