Cyclic FAP-Targeting Peptide Conjugates for Precise Tumor Delivery

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Solution Overview

Problem

There is a need for an effective means of treating cancer by targeting Fibroblast Activation Protein (FAP) using radiolabeled compounds.

Innovation Solution

Development of a conjugate that binds to FAP, comprising a chelator or cytotoxic drug attached to a molecule containing a cyclic peptide, which releases radiation or cytotoxic drugs at the tumor site.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If FAP is used as a therapeutic target for cancer treatment, then treatment specificity is improved, but delivery precision and therapeutic efficacy are insufficient

Engineering Contradiction:

Improvetreatment specificityVSAvoiddelivery precision

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The invention divides the FAP protein into specific epitope regions (amino acid sequences) that can be independently targeted by peptide conjugates. By segmenting the target protein into specific binding sites, the patent achieves precise delivery to FAP-expressing cells while maintaining treatment specificity, resolving the contradiction between reliability and manufacturing precision.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses peptide conjugates as intermediary molecules that bridge the gap between the radiopharmaceutical and FAP target. These conjugates act as mediators that specifically bind to FAP epitopes and deliver the therapeutic payload, enhancing delivery precision while maintaining treatment specificity through the intermediary peptide-FAP interaction.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If radiolabeled compounds are used to target FAP, then therapeutic efficacy is improved, but the complexity of conjugate design and preparation increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidconjugate design complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention segments the conjugate design into modular components: defined peptide sequences targeting specific FAP epitopes, chelator moieties for radionuclide binding, and linker regions. This modular segmentation simplifies the design process while maintaining therapeutic efficacy, as each component can be independently optimized and assembled.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs parameter changes in the peptide sequence (amino acid composition, length, cyclization) and chelator properties to optimize the conjugate for therapeutic efficacy. By systematically varying these parameters, the patent achieves effective FAP targeting and radiopharmaceutical stability without excessive design complexity.

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If peptide conjugates are designed to bind FAP, then binding affinity is improved, but the stability of the conjugate-protein complex and metabolic stability are insufficient

Engineering Contradiction:

Improvebinding affinityVSAvoidcomplex stability

Core Design Contradiction:

Measurement precisionVSStability of the object's composition

Solution Approach 1:

The invention employs nested structural design where the peptide sequence is cyclized to form a stable core structure, and the chelator is nested within the conjugate architecture. This nesting provides structural stability to the complex while maintaining high binding affinity through the peptide-FAP interaction, resolving the contradiction between measurement precision and stability.

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent creates a composite conjugate structure combining peptide, chelator, and linker components with optimized properties. This composite design enhances both binding affinity (through peptide-FAP interaction) and stability (through chelator-radionuclide complex and conjugate structure), simultaneously addressing both requirements.

Inventive Principle:

Principle #40Composite materials

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 conjugate effectively targets cancer cells and tumor stromal cells, providing precise delivery of radiation or cytotoxic drugs for therapeutic treatment.

Implementation Method 1

C is a chelator that stably complexes (i.e., binds tightly) a radionuclide

Methodology Applied

Scientific EffectChelation:

Implementation Method 2

T is a targeting molecular structure that is designed to bind to diseased cells, often by binding to a cell surface receptor

Methodology Applied

Scientific EffectMolecular recognition:

Implementation Method 3

a radionuclide that decays by various forms of radioactive decay modes

Methodology Applied

Scientific EffectRadioactive decay: Radioactive Decay

Data Source

PatentUS12514938B2Fibroblast activation protein targeting peptides

Publication Date: 2026.01.06 PERSPECTIVE THERAPEUTICS INC

AI summary

The present invention relates to a fibroblast activation protein alpha (FAP)-targeting peptides A-[Z-AA1-AA2-AA3-AA4-AA5-AA6-AA7-Z]-B. A is N-terminal structure. B is C-terminal structure, and each of the Z, AA1, AA2, AA3, AA4, AA5, AA6, AA7 is a residue of an amino acid. The peptides can be linear or cyclized.