Cyclic Peptides Targeting SorCS1-3 Receptors
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Solution Overview
Problem
Current treatments for neurodegenerative diseases lack effectiveness, and there is a need for novel agents that can target specific pathways mediated by SorCS1-3 receptors to treat neurodegenerative diseases, neuropathic pain, mental and behavioral disorders, stroke, and metabolic disorders with high potency, selectivity, improved safety, and desirable pharmacokinetic parameters.
Innovation Solution
Development of seven novel cyclic peptides derived from the C-terminal cytoplasmic domain of SorCS1, SorCS2, and SorCS3 receptors, which activate CREB and increase the clearance of misfolded proteins, thereby promoting neuronal survival and lysosomal function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for neurodegenerative diseases, then current standard therapy is maintained, but treatment effectiveness is insufficient and no cure exists
Solution Approach 1:
The patent modifies the molecular structure of peptide ligands by changing amino acid sequences, cyclization patterns, and post-translational modifications to optimize binding affinity and signaling efficacy. This parameter optimization enables the peptides to effectively activate CREB and enhance lysosomal function, directly addressing the insufficiency of conventional treatments.
Solution Approach 2:
The cyclic peptides act as intermediary molecules that bridge the gap between neurotrophic factors and downstream signaling pathways. By serving as potent activators of CREB and modulators of lysosomal function, these peptides mediate the therapeutic effects, enabling treatment effectiveness where conventional therapies fail.
2Manufacturing precision
If novel agents are developed to target SorCS1-3 receptors, then treatment selectivity and potency are improved, but development complexity increases
Solution Approach 1:
The patent divides the complex task of developing neurodegenerative disease treatments into discrete peptide sequences derived from specific receptor domains (SorCS1-3 cytoplasmic regions). By segmenting the target area and designing peptides to match specific segments, the invention achieves high target specificity while managing design complexity through modular approaches.
Solution Approach 2:
The invention focuses on the local cytoplasmic domain of SorCS1-3 receptors, designing peptides with specific amino acid sequences that match this localized region. This local quality approach enables precise targeting of the receptor's functional domain, improving selectivity while keeping the overall design strategy manageable through concentration on a specific molecular region.
3Reliability
If peptide compounds are used to activate CREB and enhance lysosomal function, then neuronal survival is improved, but pharmacokinetic parameters must be optimized for clinical use
Solution Approach 1:
The patent optimizes peptide parameters including cyclization (head-to-tail, side-chain to side-chain), amino acid sequence variations, and post-translational modifications to extend half-life and improve pharmacokinetic properties. These parameter changes enable the peptides to maintain neuronal survival effects while achieving desirable duration of action for clinical application.
Solution Approach 2:
The invention creates composite peptide structures combining different amino acid residues, cyclization patterns, and chemical modifications to achieve optimal pharmacokinetic properties. These composite designs integrate multiple functional elements within a single peptide molecule, simultaneously achieving neuronal survival promotion and improved half-life for clinical use.
Data Source
AI summary
The present invention concerns novel cyclic peptides, and medical uses thereof, such as treatment and/or prevention of diseases of the nervous system, neuropathic pain, and/or mental and behavioural disorders, and related aspects.