In the competitive world of biopharmaceutical manufacturing, efficiency, consistency, and scalability are essential. One of the most critical factors in monoclonal antibody (mAb) production is the optimization of cell culture media, where even minor improvements can translate into significant gains. Evonik’s cQrex^® peptides offer a scientifically advanced, flexible solution that directly addresses the limitations of traditional amino acids in media formulation. The result: higher yields, simplified feeds, and enhanced process reliability.

Addressing Amino Acid Instability with Peptide Precision

Cell culture scientists have long struggled with the low solubility, instability and degradation of certain amino acids, namely L-glutamine, L-tyrosine, and L-cysteine, when used in chemically defined media. These amino acids are critical for cell viability and productivity, but their limitations compromise process performance and often necessitate complex dual-feed systems with a pH-neutral feed as well as an alkaline feed to solubilize for example L-tyrosine and L-cysteine.

The cQrex^® portfolio offers an alternative by delivering these amino acids in peptide forms, which are both highly stable and soluble in the cell culture medium at neutral pH. They improve the media shelf life, eliminate the need for extreme pH adjustments and ensure handling safety.

Inside the cQrex^® Portfolio: Innovative Solutions for Media Challenges

Evonik’s cQrex^® peptides are chemically defined and bioavailable sources of essential amino acids known to be problematic in traditional media due to low solubility or instability. They are not just substitutes—they are high-quality ingredients with improved solubility, stability, and bioprocess compatibility designed to boost cell culture performance. When used individually or in combination, the peptides offer biomanufacturers the ability to:

• Supply key amino acids to cells without stability or solubility limitations
• Ensure cell viability and growth
• Drive cell productivity and overall performance

This peptide-driven approach to media design unlocks greater control and flexibility in upstream processing—especially critical as monoclonal antibody pipelines and titers continue to rise. Below is a breakdown of each peptide and its targeted role in cell culture media design.

Glutamine Peptides – Stabilizing a Critical Growth Driver

L-Glutamine is a vital energy source and nitrogen donor, but it is chemically unstable in solution, especially at neutral pH. It spontaneously degrades and leads to the formation of ammonia, which is toxic to cells and negatively impacts protein production.

• cQrex^® AQ – L-Alanyl-L-glutamine
  This dipeptide stabilizes L-glutamine by forming a bond with L-alanine. It releases glutamine enzymatically inside the cell, reducing extracellular degradation and ammonia buildup. It is ideal for long-term cultures or perfusion processes.
• cQrex^® GQ – Glycyl-L-glutamine hydrate
  An alternative glutamine peptide with glycine instead of L-alanine, offering different metabolic profiles. Like cQrex^® AQ, cQrex^® GQ enhances glutamine stability while maintaining bioavailability under physiological pH conditions.

Application: Use glutamine peptides as supplements or replacement of L-glutamine in media to reduce formation of toxic byproducts and extend media shelf life.

Tyrosine Peptides – Solving Solubility Issues

Tyrosine is notoriously poorly soluble at neutral pH, often requiring the addition of an alkaline feed in a fed-batch process, which complicates bioprocessing and increases operational risk.

• cQrex^® AY – L-Alanyl-L-tyrosine trihydrate
  This peptide increases the solubility of L-tyrosine by binding it with L-alanine. It is stable in aqueous solution and can be used in feed or basal media without pH adjustment.
• cQrex^® GY – Glycyl-L-tyrosine dihydrate
  Particularly relevant for cell lines that are sensitive to L-alanine, as an alternative to cQrex^® AY. It allows media formulators to maintain a neutral pH, eliminating the need for separate tyrosine supply with an alkaline feed.

Application: Use tyrosine peptides as supplements or partial replacement of L-tyrosine in basal and/or feed media to eliminate solubility hurdles and make this crucial amino acid available to cells.

Cystine Peptides – Managing Redox Sensitivity

L-Cysteine is essential for protein synthesis and maintaining redox balance but is highly unstable and prone to oxidation into L-cystine in media. This instability often necessitates preparation of fresh solutions or feeds with alkaline pH.

• cQrex^® AC – N,N’-di-L-Alanyl-L-cystine
  This peptide is a more stable and soluble form of L-cysteine, which is stabilized via peptide linkage to L-alanine.
• cQrex^® KC – N,N’-di-L-Lys-L-CySS 2HCl H₂O
  A highly specialized peptide composed of L-lysine and L-cystine. cQrex^® KC offers excellent solubility, enabling its use in single, neutral-pH feed systems—a major operational advantage.

Application: Use cystine peptides as supplements or partial replacement of L-cysteine or L-cystine in basal and/or feed media to reduce oxidation risk and supply sufficient nutrients to cells.

Intensification: Higher Titers, Healthier Cells

The true power of the cQrex^® platform lies in its ability to intensify production without sacrificing quality or requiring major process changes. Peptides enable higher nutrient concentrations and sustained availability, directly supporting:

• Enhanced cell growth
• Improved cell viability and viable cell density (VCD)
• Elevated mAb titers

This makes cQrex^® an ideal solution not just for media optimization but for full process intensification, especially in high-demand therapeutic protein production settings.

Simplification: From Dual-Feed to Single-Feed Systems

One of the standout advantages of cQrex^® peptides is their ability to simplify complex feeding strategies. For example, using cQrex^® GY and cQrex^® KC in a fed-batch process allows formulators to eliminate the alkaline feed entirely, enabling a single-feed system at neutral pH. This simplification offers:

• Reduced need for pH control and feed conditioning
• Lower operational complexity and risk
• Pathway to time and cost savings

In practice, this shift can significantly streamline the bioprocess with lower production costs, cutting down on materials, time, and potential failure points while maintaining—or even increasing—mAb productivity. Case studies show that the single-feed strategy based on cQrex^® peptides allows for comparable cell viability and VCD while strongly improving titers in CHO cell culture.

Flexible Formulation: Customize or Optimize

Whether you’re formulating a new medium from scratch or enhancing an existing commercial product, cQrex^® peptides are designed to plug seamlessly into your workflow.

Two key application approaches:

1. Supplements to Existing Media
   Example: Add cQrex^® GY to commercially available basal media to boost cell productivity and reach higher mAb titers
2. Replacement of Challenging Amino Acids
   Example: Replace unstable L-cysteine with cQrex^® KC to ensure sufficient nutrient supply throughout the bioprocess.

Because these peptides are highly soluble and stable, they reduce the need for aggressive solubilization techniques and stock solutions can be prepared in advance, offering broader formulation freedom and bioprocess flexibility across platforms.

Why cQrex^® Peptides Matter

As biologics pipelines grow more complex, upstream process control becomes more critical than ever. The cQrex^® peptide portfolio addresses longstanding formulation challenges while opening new doors for process innovation and cell culture performance improvement.

Higher productivity driven by the cQrex® peptides means a lower number of production runs required to reach the desired quantity of end product. Additionally, they enable highly concentrated media and encourage the transition from a dual to a single-feed system, allowing for savings in equipment, time and energy. The double-sided benefits of formulating media with cQrex® peptides lead to more efficient production of biopharmaceuticals with lower overall production cost and can be correlated to a more sustainable bioprocess.

With cQrex^®, you gain:

• Higher productivity through improved nutrient availability
• Simpler operations via feed consolidation and neutral pH compatibility
• Regulatory confidence with chemically defined, highly pure and animal-free ingredients

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