Peptides Modulating LSD2 Demethylase Activity

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Solution Overview

Problem

Current understanding of histone demethylase regulation is limited, particularly regarding cofactors that enhance enzymatic activity on nucleosomal substrates, and their role in diseases such as cancer, where LSD2 plays a significant role in cell proliferation and reproductive biology.

Innovation Solution

Discovery of short peptides derived from NPAC/GLYR1 that modulate LSD2 enzymatic activity and biological function, including peptides that stimulate or inhibit LSD2 demethylase activity, and antibodies targeting the interaction between LSD2 and NPAC to treat diseases like cancer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If LSD2 enzymatic activity is enhanced to treat diseases, then therapeutic effect is improved, but cell proliferation control is worsened

Engineering Contradiction:

Improvetherapeutic effectVSAvoidcell proliferation control

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs peptides as intermediary molecules that specifically bind to LSD2 and modulate its enzymatic activity. These peptide intermediaries allow precise control of LSD2 function, enabling therapeutic effects while maintaining cell proliferation control through regulated demethylase activity rather than uncontrolled enhancement

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention utilizes peptides that induce conformational changes in LSD2 or its interaction partners (like NPAC) to modulate enzymatic activity. By changing the structural parameters of the protein complex through peptide binding, the system achieves controlled demethylation activity that provides therapeutic benefits without disrupting cell proliferation regulation

Inventive Principle:

Principle #35Parameter changes

2Productivity

If cofactors are identified to enhance demethylase activity on nucleosomal substrates, then enzymatic efficiency is improved, but understanding of regulatory mechanisms is worsened

Engineering Contradiction:

Improveenzymatic efficiencyVSAvoidregulatory mechanism understanding

Core Design Contradiction:

ProductivityVSLoss of information

Solution Approach 1:

The patent segments the regulatory system into distinct functional components: the demethylase enzyme (LSD2), the cofactor (NPAC), and the nucleosomal substrate. By studying their individual and combined functions, the research enhances enzymatic efficiency while maintaining understanding of regulatory mechanisms through systematic analysis of each component's role

Inventive Principle:

Principle #1Segmentation

3Reliability

If short peptides are used to modulate LSD2 activity, then treatment specificity is improved, but molecular mechanism complexity is worsened

Engineering Contradiction:

Improvetreatment specificityVSAvoidmolecular mechanism complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts the key regulatory interaction between LSD2 and its cofactor NPAC, and further extracts the essential binding interface to design short peptide modulators. By taking out only the critical functional elements needed for LSD2 regulation, the invention achieves treatment specificity while simplifying the molecular mechanism compared to using full-length proteins

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS9745384B2Peptides useful for modulating histone demethylase function

Publication Date: 2017.08.29 THE BRIGHAM & WOMEN S HOSPITAL INC

AI summary

We described peptides and peptide fragments that can be used to inhibit cyclin D1 and cyclin E1, function of both of which is involved in malignant growth. Methods of treatment of cancer by inhibiting interaction between NPAC and LSD2 are also provided.