Aromatic Cationic Peptides for Energy-Independent Cell Delivery

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for delivering molecules into cells face challenges due to limited cell membrane permeability, energy-dependent endocytosis, toxicity, and immune responses associated with large peptides, making it difficult to achieve effective therapeutic, prophylactic, and diagnostic applications.

Innovation Solution

Aromatic cationic peptides with specific charge and length characteristics are used to form carrier complexes that can cross cell membranes energy-independently, ensuring delivery of molecules into the cell while being peptidase-resistant and non-toxic.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If protein transduction domains (PTDs) are used to deliver compounds into cells, then cell membrane crossing capability is improved, but the delivery mechanism becomes energy-dependent endocytosis which confines compounds to endosomal vesicles

Engineering Contradiction:

Improvecell membrane crossing capabilityVSAvoiddelivery mechanism complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent modifies the chemical structure of cell penetrating peptides by incorporating D-amino acids and specific amino acid sequences (such as Dmt1-DALDA) to change the delivery mechanism from energy-dependent endocytosis to energy-independent diffusion, allowing compounds to reach the cytoplasm directly

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite peptide structures combining D-amino acids with specific aromatic and basic residues to achieve both membrane permeability and cytoplasmic delivery, resulting in peptides that are resistant to proteolysis and toxic while maintaining effective compound delivery

Inventive Principle:

Principle #40Composite materials

2Reliability

If larger peptides are used to cross cell membranes, then membrane crossing capability is improved, but immune responses and toxicity increase

Engineering Contradiction:

Improvemembrane crossing capabilityVSAvoidtoxicity and immune responses

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent divides the peptide into optimized segments with specific functions: D-amino acid residues for protease resistance, aromatic residues for membrane interaction, and basic residues for charge-mediated delivery, creating a compact 6-12 amino acid sequence that minimizes immunogenicity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention uses short-lived, small-molecule peptides (6-12 amino acids) rather than large proteins, making them less immunogenic and easier to clear from the body, while still achieving effective cell penetration and compound delivery

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Productivity

If conventional peptides are used for molecule delivery, then delivery capability is improved, but peptidase susceptibility increases reducing effectiveness

Engineering Contradiction:

Improvemolecule delivery effectivenessVSAvoidpeptide stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent changes the stereochemistry of amino acid residues from L-form to D-form, making the peptide backbone resistant to proteolysis by cellular peptidases while maintaining the ability to interact with cell membranes and deliver compounds effectively

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS7704954B2Method and carrier complexes for delivering molecules to cells

Publication Date: 2010.04.27 CORNELL RES FOUNDATION INC

AI summary

The invention relates to carrier complexes and methods for delivering molecules to cells. The carrier complexes comprises a molecule and an aromatic cationic peptide in accordance with the invention. In one embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a carrier complex. In another embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a molecule and an aromatic cationic peptide.