C4S Proteoglycan Transporter Peptides
Solution Overview
Problem
Current methods for intracellular delivery of biologically active molecules face challenges due to the impermeability of cellular membranes and the lack of specificity and stability of existing cell-penetrating peptides, leading to limited therapeutic and diagnostic efficacy.
Innovation Solution
Development of specific consensus sequences of peptides and polypeptides that selectively bind to chondroitin-4-sulfate proteoglycans, ensuring targeted and stable delivery of conjugated molecules into cells by maintaining a specific 3D arrangement of arginine residues, which enhances in vivo stability and reduces non-specific interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If viral or bacterial peptides (CPPs) are used for intracellular delivery, then membrane penetration capability is improved, but in vivo stability deteriorates due to rapid protease degradation
Solution Approach 1:
The patent applies parameter changes by systematically varying amino acid sequences to identify consensus sequences with enhanced stability. Specifically, the invention uses a library approach testing different amino acid compositions and arrangements to find sequences that resist protease degradation while maintaining membrane penetration capability, thereby resolving the contradiction between penetration efficiency and in vivo stability.
Solution Approach 2:
The patent employs composite materials by creating hybrid peptide structures that combine stable amino acid motifs with functional delivery domains. The consensus sequences identified in the patent represent composite structures that integrate protease-resistant elements with cell-penetrating capabilities, achieving both stability and functionality simultaneously.
2Reliability
If cationic peptides rich in basic residues are used for cell penetration, then membrane binding activity is improved, but specificity for particular cell types deteriorates
Solution Approach 1:
The patent applies local quality by introducing specific amino acid motifs at particular positions within the peptide sequence. The consensus sequences contain localized basic residue clusters that provide membrane binding activity at specific sites, while other regions contribute to specificity, thereby resolving the contradiction between binding strength and cell type selectivity.
Solution Approach 2:
The patent employs segmentation by dividing the peptide into functional domains: N-terminal regions with basic residues for membrane binding, central regions for stability, and C-terminal regions for cargo attachment. This segmentation allows each domain to optimize its function independently, achieving both strong binding and specificity.
3Duration of action of stationary object
If stabilized peptides with non-natural amino acids are used, then in vivo stability is improved, but toxicity increases with systemic administration
Solution Approach 1:
The patent applies parameter changes by optimizing the ratio and arrangement of natural versus non-natural amino acids. The consensus sequences use predominantly natural amino acids with selective incorporation of stabilizing motifs, achieving enhanced stability while maintaining biocompatibility and reducing systemic toxicity compared to fully synthetic stabilized peptides.
4Reliability
If existing transporter constructs are used for cargo delivery, then trans-membrane transport activity is improved, but cargo-transporter cleavage efficiency deteriorates
Solution Approach 1:
The patent applies the taking out principle by designing consensus sequences that facilitate spontaneous dissociation of the cargo-transporter complex after delivery. The specific amino acid composition and structure of the consensus sequences enable efficient cleavage or release of the cargo moiety from the transporter, resolving the contradiction between maintaining transport integrity and enabling cargo release.
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 peptides and polypeptides with consensus sequences achieve selective targeting and delivery of biologically active molecules to cells expressing chondroitin-4-sulfate, improving the therapeutic and diagnostic potential while minimizing side effects.
Implementation Method 1
specific consensus sequences of isolated peptides and/or polypeptides are able to effect specific binding to the proteoglycan C4S
Data Source
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AI summary
The present invention relates to isolated molecules, peptides, and polypeptides of specific consensus sequences or structures, and to compounds comprising or consisting of such molecules, peptides and polypeptides, which may act as transporter molecules that specifically recognize proteoglycans, in particular, chondroitin-4-sulfate (C4S). The isolated molecules, peptides, polypeptides and compounds of the invention may be conjugated or otherwise linked to a biologically active moiety (BAM). Thus the BAM conjugates allow the specific targeting and delivery of the BAM, which may be, for example, a peptide, chemical entity or nucleic acid, into the cytoplasm and/or nuclei of C4S expressing cells in vitro and in vivo.