Disulfide-Linked Peptide Dimers for Targeted Drug Delivery
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Solution Overview
Problem
Current cell penetrating peptides face challenges such as short circulating plasma half-lives, low permeability, and metabolic instability, limiting their effectiveness as drug carriers due to issues like rapid proteolysis and limited residence time in tissues, which complicates targeted drug delivery and increases side effects in cancer treatment.
Innovation Solution
The development of a cell penetrating peptide dimer (CPPecp-dimer) with a disulfide linkage, which enhances stability, reduces proteolysis, and increases selective heparan sulfate binding activity, allowing for improved intracellular delivery and retention of therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If natural peptides are used as cell penetrating peptides, then cell penetration capability is achieved, but circulating plasma half-life is short and metabolic stability is low
Solution Approach 1:
The patent combines two CPPecp monomers into a dimer structure through disulfide linkage. This merging of two peptide units creates a more stable complex that resists proteolytic degradation while maintaining cell penetration capability. The disulfide bond provides structural stability and extends circulating half-life without sacrificing the inherent cell-penetrating properties of the individual peptide units.
Solution Approach 2:
The patent creates a composite peptide structure by forming a dimer of CPPecp units linked through disulfide bonds. This composite structure combines the advantages of individual peptides while introducing enhanced stability and reduced metabolic degradation. The disulfide-linked dimer represents a composite material approach that improves pharmacokinetic properties while maintaining biological activity.
2Reliability
If peptide stability is enhanced through modification, then proteolysis resistance increases, but permeability and cellular uptake may be reduced
Solution Approach 1:
By merging two CPPecp monomers into a dimer through disulfide linkage, the patent achieves enhanced stability without compromising permeability. The disulfide bond provides structural integrity and proteolysis resistance, while the combined structure maintains the cell-penetrating characteristics of the individual units, potentially enhancing uptake through increased avidity for cellular receptors.
Solution Approach 2:
The patent modifies the peptide structure by changing the oligomeric state from monomer to dimer and introducing disulfide bonds. This parameter change in molecular weight, structure, and bonding type enhances stability and proteolysis resistance. The specific modification of forming inter-peptide disulfide bonds maintains the basic amino acid residues necessary for cellular interaction while providing structural stability.
3Reliability
If disulfide linkage is formed to improve stability, then proteolytic resistance increases, but manufacturing complexity increases
Solution Approach 1:
The patent combines two CPPecp monomers through disulfide linkage to achieve proteolytic resistance. This merging approach provides a straightforward strategy for improving stability that can be implemented through oxidative conditions during peptide synthesis or purification. The disulfide bond formation is a well-established chemical reaction that can be integrated into existing peptide manufacturing workflows.
Solution Approach 2:
The patent employs parameter changes by controlling oxidation conditions to form disulfide bonds between cysteine residues of CPPecp monomers. This chemical modification can be achieved through simple oxidative treatment during or after peptide synthesis, avoiding the need for complex multi-step manufacturing processes. The approach leverages standard peptide chemistry techniques to introduce the stabilizing disulfide linkage.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The CPPecp-dimer exhibits significantly increased stability and maintained cell penetration and heparan sulfate binding affinity, making it a promising candidate for targeted drug delivery with reduced toxicity and enhanced therapeutic efficacy.
Implementation Method 1
Oxidative modification improves the drugability of cell penetrating peptides as drug carriers
Implementation Method 2
a cell penetrating peptide dimer having disulfide linkage
Implementation Method 3
the motif located within the CPPecp shows heparin or heparan sulfate binding activity
Data Source
AI summary
The present invention provides a cell penetrating peptide dimer by oxidative modification, in which each monomer is connected with each other by the disulfide linkage. The drugability of the peptide dimer has been improved through enhancing stability, reducing proteolysis, retaining permeability and increasing heparan sulfate binding specificity. The modified peptide products can be used to deliver drug molecules as a suitable drug carrier for targeted therapy.