Dipeptide-Trace Metal Complexes for Cell Culture Media

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Solution Overview

Problem

Current cell culture media face challenges in balancing the supply of trace metals like copper and zinc, which are essential for cell growth and productivity, while avoiding toxicity, especially when cysteine participates in redox reactions that form reactive oxygen species, and cysteine has low solubility and stability issues.

Innovation Solution

Incorporating dipeptides composed of cysteine and other natural amino acids into the cell culture media, with a specific molar ratio to trace metal ions, reduces toxicity and enhances stability, allowing for higher concentrations of trace metals and cysteine without adverse effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cysteine is added to cell culture media to support cell growth and metabolism, then cell viability and productivity are improved, but solubility and stability problems occur due to low water solubility and reactive thiol group instability

Engineering Contradiction:
Improvecell viabilityVSAvoidcysteine stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent combines cysteine with another amino acid to form a dipeptide structure. This composite approach maintains the beneficial biological activity of cysteine while improving its solubility and stability characteristics through the peptide bond formation, resolving the contradiction between cell viability enhancement and compositional stability.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent changes the chemical form of cysteine from free amino acid to dipeptide conjugate. This parameter change in molecular structure fundamentally alters solubility and stability properties while preserving the essential biological function of cysteine in supporting cell growth and metabolism.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If trace metal ions are added to cell culture media to support metabolism and productivity, then cell growth and product formation are improved, but toxicity occurs when provided in excess amounts

Engineering Contradiction:
Improveproduct formationVSAvoidmetal ion toxicity
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces dipeptides as intermediary molecules that mediate between trace metal ions and cellular components. The dipeptides act as chelating agents that bind metal ions, controlling their availability and preventing toxic interactions while maintaining essential metabolic functions, thus resolving the contradiction between productivity enhancement and toxicity prevention.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Manufacturing precision

If chemically defined, serum-free media are used to increase safety and consistency, then product quality is improved, but it becomes difficult to balance sufficient trace element supply against toxic effects

Engineering Contradiction:
Improveproduct quality consistencyVSAvoidmedia formulation complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent changes the chemical form and delivery mechanism of trace elements by incorporating them into dipeptide structures. This parameter change simplifies the overall media formulation by creating stable, bioavailable complexes that are easier to balance and control, reducing the complexity of achieving safe and effective trace element supplementation in chemically defined media.

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 use of dipeptides suppresses metal-induced toxicity, increases cellular viability, and enables the formulation of highly concentrated, chemically defined media for intensified biopharmaceutical production processes.

Implementation Method 1

L-cysteine participates in redox reactions with metal ions and contributes to ROS formation. In these reactions, L-cysteine is oxidized to the disulfide form L-cysteine.

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Data Source

PatentUS20240279615A1Compositions comprising dipeptides and trace elements
Publication Date: 2024.08.22 EVONIK OPERATIONS GMBH
  • US20240279615A1 patent drawing
  • US20240279615A1 patent drawing
  • US20240279615A1 patent drawing

AI summary

Compositions that have dipeptides, trace metal ions, and a molar ratio between 10000 and 20 can be used in a cell culture medium. More specifically, improved culture media for use in biotechnological production processes, processes employing such improved media, and to products obtained from the processes using the improved culture media.