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Protamine as an efficient membrane-translocating peptide.

Fred Reynolds1, Ralph Weissleder, Lee Josephson

  • 1Center for Molecular Imaging Research, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02129, USA.

Bioconjugate Chemistry
|September 22, 2005
PubMed
Summary
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Tetramethylrhodamine-labeled protamine (Pro(Rh)) demonstrates similar cellular uptake and nuclear localization as the tat peptide. Attaching protamine to nanoparticles significantly enhanced cellular uptake, suggesting protamine

Area of Science:

  • Bioconjugation and Pharmaceutical Development
  • Cellular Biology and Drug Delivery

Background:

  • Protamine, a positively charged protein from salmon roe, has established pharmaceutical applications.
  • Membrane-translocating peptides are crucial for developing novel drug delivery systems.
  • Understanding protamine's cellular interactions is key for its pharmaceutical potential.

Purpose of the Study:

  • To label protamine with tetramethylrhodamine for fluorescent tracking (Pro(Rh)).
  • To investigate the cellular internalization and nuclear localization of Pro(Rh).
  • To evaluate protamine's potential in designing novel drug delivery systems.

Main Methods:

  • Protamine was conjugated with tetramethylrhodamine N-hydroxysuccinimide ester.
  • Cellular uptake and nuclear localization of Pro(Rh) were compared with fluorescein-labeled tat peptide (Tat(Fl)).

Related Experiment Videos

  • Pro(Rh) was covalently attached to amino-CLIO nanoparticles to assess nanoparticle cellular uptake.

    • Main Results:

    • Pro(Rh) exhibited time- and concentration-dependent cellular internalization, mirroring Tat(Fl).
    • Both Pro(Rh) and Tat(Fl) showed strong nuclear localization in HeLa and CaCo-2 cells.
    • Conjugation of Pro(Rh) to nanoparticles significantly enhanced cellular uptake.

    Conclusions:

    • Protamine shares functional similarities with known membrane-translocating peptides.
    • Protamine holds promise for developing novel pharmaceuticals targeting cellular translocation and nuclear delivery.
    • Fluorescently labeled protamines can serve as valuable tools for studying pharmaceutical interactions.