Cyclic Peptide Crystallization with Standardized Organic Solvents

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

There is a need for a general and simple technology to efficiently produce and screen crystals of cyclic peptides containing N-substituted amino acids, as existing methods rely on trial and error and lack a standardized approach.

Innovation Solution

A method involving bringing a cyclic peptide into contact with a specific solvent, such as amide-based, sulfoxide-based, or aromatic hydrocarbon-based solvents, to produce crystals with defined characteristics, including diffraction peaks in X-ray diffraction, using solvents with molecular weights between 18 and 170, and optionally including surfactants or PEG-based solvents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If trial and error method is used to find optimal crystallization conditions for each cyclic peptide, then crystal production is possible, but the process becomes time-consuming and lacks efficiency

Engineering Contradiction:
Improvecrystal production efficiencyVSAvoidtime for condition optimization
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent establishes a universal crystallization method using organic solvents that can be applied to multiple cyclic peptides containing N-substituted amino acids simultaneously, eliminating the need for individual trial-and-error optimization for each peptide. This multi-functional approach allows the same solvent-based protocol to work across different cyclic peptide structures, dramatically improving productivity while reducing time investment.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention identifies specific solvent parameters (molecular weight range, solvent type) that control crystallization outcomes. By changing the solvent parameter from water to specific organic solvents with defined molecular weights, the method achieves reliable crystal formation without time-consuming iterative optimization, directly resolving the productivity-time contradiction.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If conventional crystallization methods are used for cyclic peptides, then crystals can be obtained, but the process requires complex procedures including column chromatography

Engineering Contradiction:
Improvesimplicity of crystallization processVSAvoidcomplexity of purification equipment
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the column chromatography step from the traditional purification process. By using organic solvents that directly induce crystallization of cyclic peptides, the method removes the need for complex chromatographic equipment and procedures, significantly simplifying the manufacturing process while maintaining effective purification.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces organic solvents as intermediary substances that mediate between the cyclic peptide and the crystallization process. These solvents act as intermediaries that facilitate direct crystal formation without requiring complex purification equipment, thereby reducing device complexity while improving ease of manufacture.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If no standardized crystallization method is available for cyclic peptides with N-substituted amino acids, then crystal production is possible through individual optimization, but the lack of standardization reduces reproducibility and efficiency

Engineering Contradiction:
Improvereproducibility of crystal productionVSAvoidefficiency of crystal production
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent creates a standardized universal protocol using organic solvents that ensures reproducible crystal production across different cyclic peptides. This standardized approach eliminates variability associated with individual optimization, improving reliability while the efficiency of the standardized protocol simultaneously enhances productivity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention establishes specific solvent parameters (organic solvent type, molecular weight range) as standardized conditions that ensure reproducible results. By fixing these parameters in advance, the method achieves both high reliability through reproducibility and high productivity through eliminated optimization steps.

Inventive Principle:
Principle #35Parameter changes

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

This method allows for the efficient production and screening of cyclic peptide crystals, eliminating the need for column chromatography and providing a standardized approach applicable to various cyclic peptides.

Implementation Method 1

bringing a cyclic peptide into contact with a solvent

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 2

produce crystals with defined characteristics, including diffraction peaks in X-ray diffraction

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 3

have one or more diffraction peaks in powder X-ray diffraction using CuKα radiation

Methodology Applied
Scientific EffectX-ray diffraction: X-Ray

Implementation Method 4

diffraction peaks in powder X-ray diffraction

Methodology Applied
Scientific EffectDiffraction: Diffraction

Data Source

PatentEP4585605A1Method for producing cyclic peptide crystals
Publication Date: 2025.07.16 CHUGAI PHARMA CO LTD
  • EP4585605A1 patent drawingFigure 1(A)~1(E)
  • EP4585605A1 patent drawingFigure 2(A)~2(E)
  • EP4585605A1 patent drawingFigure 3(A)~3(E)

AI summary

There is disclosed a method for producing cyclic peptide crystals, the method comprising a step of bringing a cyclic peptide into contact with a specific solvent.