Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

The engineering of membrane-permeable peptides.

Christina N Carrigan1, Barbara Imperiali

  • 1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Analytical Biochemistry
|May 24, 2005
PubMed
Summary

Researchers developed labile lipid motifs for enhanced peptide delivery into cells. These modifications improve cell uptake by increasing lipophilicity and optimizing charge distribution, aiding peptide therapeutics.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Glycoconjugate diversification in <i>Campylobacter concisus</i> is determined by two glycosyltransferases.

bioRxiv : the preprint server for biology·2026
Same author

Detergent Exchange from Lipid Nanoparticles into Detergent Micelles Unlocks a Tool for Biochemical and Kinetic Characterization of Membrane Proteins.

Biochemistry·2026
Same author

Detergent exchange from lipid nanoparticles into detergent micelles unlocks a tool for biochemical and kinetic characterization of membrane proteins.

bioRxiv : the preprint server for biology·2026
Same author

Correlating membrane-protein dynamics with function: Integrating bioinformatics, molecular dynamics, and single-molecule FRET.

Protein science : a publication of the Protein Society·2025
Same author

Selection of nanobodies against liponanoparticle-embedded membrane proteins by yeast-surface display.

Protein science : a publication of the Protein Society·2025
Same author

Correlating membrane-protein dynamics with function: Integrating bioinformatics, molecular dynamics, and single-molecule FRET.

bioRxiv : the preprint server for biology·2025

Area of Science:

  • Bioconjugation Chemistry
  • Cellular Delivery Systems
  • Peptide Therapeutics

Background:

  • Efficient cellular delivery of small peptides is crucial for therapeutic applications.
  • Existing peptide delivery methods often face challenges with cell membrane permeability and stability.
  • Lipid conjugation has shown promise for improving peptide delivery but requires labile linkages.

Purpose of the Study:

  • To develop and evaluate novel, reversible lipid attachment strategies for enhanced intracellular peptide delivery.
  • To synthesize and characterize fluorophore-labeled peptides incorporating labile lipid motifs.
  • To determine the key physicochemical properties influencing peptide cellular uptake efficiency.

Main Methods:

  • Development of two labile lipid motifs: cysteine dodecane disulfide (Cdd) and tyrosine/serine-myristate ester.
  • Incorporation of these motifs into peptides using Fmoc solid phase peptide synthesis.
  • Synthesis of fluorophore-labeled peptides with varied lipophilic content, net charge, and charge distribution.
  • Assessment of cellular uptake efficiency via fluorescence microscopy.

Main Results:

  • Successful synthesis of peptides with labile lipid attachments, compatible with standard peptide synthesis.
  • Demonstrated that effective cellular transport requires a net positive charge (lysine residues at termini) and a hydrophobic domain (log P ~4.0).
  • Lipid motif incorporation enhanced peptide lipophilicity and significantly contributed to cellular uptake.

Conclusions:

  • Reversible lipid attachment is a viable strategy for improving the cellular delivery of small peptides.
  • The combination of specific charge distribution and optimized hydrophobicity is critical for efficient peptide internalization.
  • Labile lipid motifs offer a method to enhance peptide lipophilicity and cell uptake with minimal impact on native peptide structure.

Related Experiment Videos