Id |
Subject |
Object |
Predicate |
Lexical cue |
T4 |
0-243 |
Sentence |
denotes |
Thymosin α1 (Tα1) is an immunostimulatory peptide for the treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and used as an immune enhancer, which also offers prospects in the context of COVID-19 infections and cancer. |
T5 |
244-407 |
Sentence |
denotes |
Manufacturing of this N-terminally acetylated 28-residue peptide is demanding, and its short plasma half-life limits in vivo efficacy and requires frequent dosing. |
T6 |
408-571 |
Sentence |
denotes |
Here, we combined the PASylation technology with enzymatic in situ N-acetylation by RimJ to produce a long-acting version of Tα1 in Escherichia coli at high yield. |
T7 |
572-687 |
Sentence |
denotes |
ESI-MS analysis of the purified fusion protein indicated the expected composition without any signs of proteolysis. |
T8 |
688-856 |
Sentence |
denotes |
SEC analysis revealed a 10-fold expanded hydrodynamic volume resulting from the fusion with a conformationally disordered Pro/Ala/Ser (PAS) polypeptide of 600 residues. |
T9 |
857-1018 |
Sentence |
denotes |
This size effect led to a plasma half-life in rats extended by more than a factor 8 compared to the original synthetic peptide due to retarded kidney filtration. |
T10 |
1019-1136 |
Sentence |
denotes |
Our study provides the basis for therapeutic development of a next generation thymosin α1 with prolonged circulation. |
T11 |
1137-1409 |
Sentence |
denotes |
Generally, the strategy of producing an N-terminally protected PASylated peptide solves three major problems of peptide drugs: (i) instability in the expression host, (ii) rapid degradation by serum exopeptidases, and (iii) low bioactivity because of fast renal clearance. |