Peptide-Based Shuttle Agents for Intracellular Drug Delivery
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Solution Overview
Problem
Existing drug discovery processes often discard small molecule drug candidates with high target binding affinity due to their diminished ability to be delivered intracellularly, limiting the use of novel therapeutic compounds.
Innovation Solution
Synthetic peptide shuttle agents with specific design parameters enhance the transduction efficiency of both proteinaceous and non-proteinaceous cargoes, including small molecule organic compounds, by facilitating their intracellular delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule drug candidates are selected based on target binding affinity, then target binding affinity is improved, but intracellular delivery ability deteriorates
Solution Approach 1:
The patent introduces a peptide shuttle agent as an intermediary carrier that binds to small molecule drug candidates and facilitates their transport across cell membranes. The shuttle agent comprises a cell-penetrating domain that enables intracellular delivery while maintaining the drug's target binding affinity, thus resolving the contradiction between high affinity and poor deliverability
Solution Approach 2:
The invention creates a composite system consisting of the small molecule drug candidate conjugated to or complexed with the peptide shuttle agent. This composite structure combines the target-binding properties of the small molecule with the cell-penetrating properties of the peptide, achieving both high affinity and improved intracellular delivery
2Adaptability or versatility
If conventional small molecule drug design is used, then drug-like physicochemical properties are maintained, but flexibility in drug design is limited
Solution Approach 1:
The patent segments the drug delivery system into two independent components: the small molecule drug candidate and the peptide shuttle agent. This segmentation allows independent optimization of each component - the drug can be designed for target affinity while the peptide is designed for cell penetration, greatly increasing flexibility in drug design without compromising manufacturability
Solution Approach 2:
The peptide shuttle agent serves as a universal delivery vehicle that can transport multiple different small molecule drug candidates with varying physicochemical properties. This multi-functionality allows the same shuttle agent to deliver diverse therapeutic compounds, expanding design flexibility across different drug candidates
Data Source
AI summary
Described herein are methods, compositions, kits and synthetic peptide shuttle agents relating to the transduction of proteinaceous and/or non-proteinaceous cargoes. The method generally comprises contacting target eukaryotic cells with a non-proteinaceous cargo and a concentration of a synthetic peptide shuttle agent sufficient to increase the transduction efficiency of the non-proteinaceous cargo, as compared to in the absence of said synthetic peptide shuttle agent. In embodiments, the non-proteinaceous cargo may be a drug, such as a small molecule drug, for treating a disease. In other embodiments, novel synthetic peptide shuttle agents having transduction activity for proteinaceous and/or non-proteinaceous cargoes are described, as well as the use of propidium iodide or other membrane-impermeable fluorescent DNA intercalating agent as a surrogate cargo for selecting versatile synthetic peptide shuttle agents having transduction activity for both proteinaceous and non-proteinaceous cargoes.