Peptide Binding Parallel-Stranded G-Quadruplexes Selectivity

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current G-quadruplex binders lack selectivity for different topologies, leading to wide-range genome effects due to structural diversity, necessitating the development of binders that can selectively discriminate between various G-quadruplex structures.

Innovation Solution

A peptide comprising or consisting of a specific amino acid sequence (SEQ ID NO:1) that selectively binds to parallel-stranded G-quadruplexes, allowing for their detection and potential use as a medicament, along with conjugates that include functional moieties for enhanced application.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional G-quadruplex binders are used, then binding to G-quadruplexes is achieved, but selectivity against different G-quadruplex topologies is lost leading to wide-range genome effects

Engineering Contradiction:

Improvebinding affinityVSAvoidoff-target effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The peptide binder is designed with specific local chemical and structural properties (amino acid composition, secondary structure elements) that are optimized to recognize and bind selectively to the specific geometry and chemical features of parallel-stranded G-quadruplexes, thereby achieving topology selectivity while maintaining binding affinity

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention changes the parameters of the binder molecule by using a peptide with specific amino acid sequence and length (16-50 residues) that confers selective binding properties to parallel-stranded G-quadruplexes, distinguishing it from conventional small molecule binders that lack topology selectivity

Inventive Principle:

Principle #35Parameter changes

2Object-generated harmful factors

If G-quadruplex structures are stabilized in telomeres and promoter regions, then anti-cancer effects are achieved, but genomic instability is promoted

Engineering Contradiction:

Improveanti-cancer effectsVSAvoidgenomic instability

Core Design Contradiction:

Object-generated harmful factorsVSObject-affected harmful factors

Solution Approach 1:

The peptide binder provides localized stabilization of G-quadruplex structures at specific genomic locations (telomeres and promoter regions of oncogenes) through selective binding to parallel-stranded topologies, enabling anti-cancer effects while avoiding non-specific genomic instability caused by conventional binders

Inventive Principle:

Principle #3Local quality

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 peptide effectively binds to parallel-stranded G-quadruplexes with high specificity, enabling their detection and providing a basis for methods to identify these structures in samples, while minimizing off-target effects.

Implementation Method 1

a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1, wherein said peptide is 16 to 50 amino acids in length and selectively binds to parallel-stranded G-quadruplexes

Methodology Applied

Scientific EffectMolecular recognition and binding:

Data Source

PatentEP2999710B1Peptides binding to parallel-stranded g-quadruplexes

Publication Date: 2019.10.02 NANYANG TECH UNIV

Figure 1
Figure 2
Figure 3

AI summary

This invention relates to a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a derivative thereof. The present invention also relates to conjugates of said peptide, the use of the peptide or the conjugate as a medicament and to methods for the detection of parallel-stranded G-quadruplexes.