Chimeric Peptides Targeting NMDA-PSD95 Interaction for Stroke Therapy

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Solution Overview

Problem

Current treatments for ischemic stroke and related central nervous system injuries are hindered by significant side effects and insufficient therapeutic efficiency, with a need for more effective neuroprotective agents that target the interaction between NMDA receptors and PSD-95.

Innovation Solution

Development of peptides, such as YEKLLDTEI or its functional variants, and chimeric peptides combining these peptides with internalization peptides like YGRKKRRQRRR, to inhibit the interaction between NMDA receptors and PSD-95, facilitating their delivery to the brain and enhancing therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional therapeutic drugs for ischemic stroke are used, then treatment coverage is provided, but significant side effects and insufficient therapeutic efficiency occur

Engineering Contradiction:

Improvetherapeutic efficiencyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses peptides (such as YEKLLDTEI) as intermediary substances that specifically bind to PSD-95 protein, blocking its interaction with NMDA receptors. This intermediary mechanism provides targeted neuroprotection without the broad-spectrum side effects of conventional drugs, resolving the contradiction between therapeutic efficiency and side effects

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the peptide structure by introducing cell-penetrating sequences (such as YGRKKRRQRRR) to change the delivery parameters of the therapeutic agent. This enables the peptide to cross the blood-brain barrier effectively, improving therapeutic efficiency while maintaining selectivity and reducing side effects

Inventive Principle:

Principle #35Parameter changes

2Reliability

If NMDA receptor interaction is inhibited to reduce excitatory neurotoxicity, then neuronal protection is improved, but delivery to brain tissue becomes challenging

Engineering Contradiction:

Improveneuronal protectionVSAvoiddelivery to brain

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent merges two functional components into a single chimeric peptide: the PSD-95 binding domain (for neuronal protection) and the cell-penetrating sequence (for brain delivery). This combination resolves the contradiction by integrating both protective efficacy and delivery capability into one molecule

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The cell-penetrating sequence acts as an intermediary that facilitates the transport of the protective peptide across the blood-brain barrier. This intermediary function enables the active component to reach its target site without requiring invasive delivery methods

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS11229675B2Therapeutic peptides for excitatory neurotoxicity-related injuries

Publication Date: 2022.01.25 BIOCELLS BEIJING BIOTECH CO LTD

AI summary

There is provided in the present application a peptide comprising the amino acid sequence of YEKLLDTEI (SEQ ID NO: 1) or a functional variant thereof. The peptide is an active peptide for the treatment of a central nervous system injury. The present application also provides a chimeric peptide comprising an active peptide and an internalization peptide. The present application also provides a pharmaceutical composition comprising the active peptide or the chimeric peptide, as well as medical use of the active peptide or the chimeric peptide.