Cyclic Peptide Metal-Complex Purification for Difficult Separation

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Solution Overview

Problem

Purification of cyclic peptides is inefficient, especially on an industrial scale, and many cyclic peptides are difficult to crystallize or purify using conventional methods like column chromatography and crystallization.

Innovation Solution

A method involving the formation of a composite of cyclic peptides with metal atoms or ions, followed by solvent mixing and separation techniques such as solid-liquid or liquid-liquid partition, to purify cyclic peptides that are challenging to crystallize.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If column chromatography is used for purification, then purification can be achieved, but efficiency is low especially on industrial scale

Engineering Contradiction:
Improvepurification efficiencyVSAvoidpurification process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention changes the physical-chemical parameters of the cyclic peptide by forming a complex with a metal atom or ion. This parameter change transforms the purification problem from a chromatographic separation challenge to a solubility-based separation, enabling efficient purification without column chromatography while maintaining high purity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces a metal atom or ion as an intermediary substance that forms a complex with the cyclic peptide. This intermediary enables the purification process by creating a composite material with altered solubility properties, allowing separation through simple filtration or decantation instead of complex chromatographic methods

Inventive Principle:
Principle #24Intermediary (Mediator)

2Device complexity

If crystallization is used for purification, then column chromatography can be avoided, but many cyclic peptides are difficult to crystallize

Engineering Contradiction:
Improvepurification process complexityVSAvoidcrystallization difficulty
Core Design Contradiction:
Device complexityVSEase of manufacture

Solution Approach 1:

The invention creates a composite material consisting of the cyclic peptide complexed with a metal atom or ion. This composite has different physical properties than the original peptide, including altered solubility and crystallization behavior, enabling purification through simple phase separation without requiring the cyclic peptide itself to crystallize

Inventive Principle:
Principle #40Composite materials

3Reliability

If conventional purification methods are used, then some cyclic peptides can be purified, but many are difficult to purify due to physical properties

Engineering Contradiction:
Improvepurification applicabilityVSAvoidpurification difficulty
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The invention universally applies parameter changes by complexing the cyclic peptide with a metal atom or ion, which fundamentally alters the physical properties of the peptide including its solubility, charge, and molecular recognition characteristics. This transformation makes purification reliable across diverse cyclic peptide structures regardless of their original difficult-to-purify properties

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

The method enables efficient purification of cyclic peptides with high purity, achieving 85% or more, by forming composites with metal atoms or ions and using solvent mixtures to separate and remove impurities effectively.

Implementation Method 1

a composite of the cyclic peptide that is a purification target or the peptide that is an impurity with a metal atom or a metal ion

Methodology Applied
Scientific EffectComplex formation: Chemical Bonding

Implementation Method 2

separating a cyclic peptide that is a purification target from a mixture containing the cyclic peptide that is a purification target as a composite with a metal atom or a metal ion

Methodology Applied
Scientific EffectLiquid-liquid partition: Liquid-Liquid Extraction

Data Source

PatentEP4631955A1Purification method and production method of cyclic peptide
Publication Date: 2025.10.15 CHUGAI PHARMA CO LTD
  • EP4631955A1 patent drawingFigure 1
  • EP4631955A1 patent drawingFigure 2a~2d
  • EP4631955A1 patent drawingFigure 3a~3d

AI summary

A purification method of a cyclic peptide, the purification method comprising the following separation step (i) or (ii): (i) separating a cyclic peptide that is a purification target from a mixture containing the cyclic peptide that is a purification target as a composite with a metal atom or a metal ion, or (ii) separating a cyclic peptide that is a purification target or a peptide that is an impurity from a mixture containing the cyclic peptide that is a purification target and the peptide that is an impurity as a composite with a metal atom or a metal ion, wherein the metal atom or metal ion is at least one selected from the group consisting of an alkali metal atom or ion, an alkaline earth metal atom or ion, a transition metal atom or ion, a poor metal atom or ion, and a rare earth metal atom or ion.