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Study · Not a test of the peptide alone · 2020

3 results

PASylated Thymosin α1: A Long-Acting Immunostimulatory Peptide for Applications in Oncology and Virology.

Binder U, Skerra A

International journal of molecular sciences24 Dec 2020Cited by 14 (Europe PMC)

Summary

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. 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. 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. ESI-MS analysis of the purified fusion protein indicated the expected composition without any signs of proteolysis. 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. 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. Our study provides the basis for therapeutic development of a next generation thymosin α1 with prolonged circulation. 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.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin alpha-1.

  1. 01AnimalNot a test of Thymosin alpha-1 aloneAnimal study (in vivo)Pharmacokinetics

    In rats, the plasma half-life of PASylated thymosin α1 was extended by more than a factor 8 compared with the original synthetic peptide.

    In plain wordsIn rats, PASylated thymosin α1 stayed in the blood more than 8 times longer than the original synthetic peptide.

    Outcome
    IncreasePlasma half-life of PASylated thymosin α1 in rats
    Study

    ratn: not reported in source

    Comparator
    Original synthetic peptide
    Outcome group
    Formulation, delivery and stability · Pharmacology

    Measurements

    Plasma half-life extension
    > 8 fold
    PASylated Tα1 versus synthetic peptide

    Source sentences

    Summary
    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.

    In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.

  2. 02LabNot a test of Thymosin alpha-1 aloneIn vitro (cell-free)Other

    In lab tests, fusion with the PAS polypeptide expanded the hydrodynamic volume of thymosin α1 about 10-fold.

    In plain wordsIn lab tests, joining thymosin α1 to a PAS chain made the molecule about 10 times larger in solution.

    Outcome
    IncreaseHydrodynamic volume of the PAS fusion
    Study

    n: not reported in source

    Purified fusion protein
    Outcome group
    Formulation, delivery and stability · Pharmacology

    Measurements

    Hydrodynamic volume expansion
    10 fold
    PAS fusion

    Source sentences

    Summary
    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.

    In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.

  3. 03LabNot a test of Thymosin alpha-1 aloneIn vitro (cell-free)Other

    In lab tests, ESI-MS showed the expected composition of the purified fusion protein without signs of proteolysis.

    In plain wordsIn lab tests, the purified fusion protein had the expected make-up and showed no signs of breakdown.

    Outcome
    Not applicableComposition and proteolysis of the purified fusion protein
    Study

    n: not reported in source

    Purified fusion protein
    Outcome group
    Formulation, delivery and stability · Pharmacology

    Source sentences

    Summary
    ESI-MS analysis of the purified fusion protein indicated the expected composition without any signs of proteolysis.

    In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    10 Oct 2026, 08:55 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 03:03 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:02 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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