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Related Concept Videos

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Site-Targeted Drug Delivery Systems: Polymeric Carriers

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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt secretion,...
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Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
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Updated: Mar 2, 2026

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Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based

D Thean1, J S Ebo1, T Luxton1

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Researchers developed cell-permeable stapled peptides to target protein interactions. A novel lipid formulation enhanced peptide delivery and efficacy, overcoming limitations for potential clinical applications.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Delivery

Background:

  • Linear peptides are limited by protease sensitivity and poor membrane permeability for intracellular targets.
  • Peptide stapling aims to improve stability and cell entry, but can cause off-target effects.
  • Targeting protein-protein interactions is crucial for cell signaling pathway modulation.

Purpose of the Study:

  • To synthesize and screen stapled peptides for Mdm2 binding and p53 activation.
  • To overcome limitations of cell permeability and serum binding in stapled peptides.
  • To enhance the efficacy of stapled peptides using lipid-based formulations.

Main Methods:

  • Synthesis and screening of a stapled peptide library.
  • Identification of a lead peptide targeting Mdm2 and activating p53.
  • Formulation of the lead peptide with a pyridinium-based cationic lipid.

Main Results:

  • A lead stapled peptide was identified with specific Mdm2 binding and p53 activation.
  • The peptide showed negligible cytotoxicity but suffered from serum avid binding.
  • Lipid formulation significantly improved peptide activity in a p53 reporter cell line via enhanced vesicular escape.

Conclusions:

  • Rigorous design can yield cell-permeable, target-specific stapled peptides.
  • Lipid formulations can improve the cell permeability and potency of stapled peptides.
  • This approach facilitates the clinical translation of stapled peptide therapeutics.