In recent years there has been a change in the ingredients used to optimize cell culture media for applications in biopharmaceutical production. Animal-derived substances are now being replaced by well-defined chemical compositions. This evolution is helping to increase the overall safety, consistency and performance of cell cullture processes - and of the drug products derived from them. Biopharmaceutical companies are looking for high purity, stability and supply security for their cell culture ingredients.
Amino acids are essential ingredients in cell culture media as they function as protein building blocks. Low stability and solubility of some amino acids like L-glutamine, L-tyrosine and L-cystine impose limits to media formulations, storage stability, process intensification and ultimately overall productivity. However, these challenges can be overcome with the replacement of such amino acids with our highly stable and soluble cQrex® peptides.
Enhancing the stability of L-Glutamine in cell culture systems
L-glutamine is a well-known example of an amino acid that exhibits limited chemical stability in cell culture media. Degradation leads to elevated levels of ammonia and glutamic acid or pyroglutamate, which have a detrimental impact on cell culture performance and product quality. This means that cell culture media containing L-glutamine cannot be stored for extended periods of time. As a consequence L-glutamine is usually added to culture media shortly before starting the cell culture process. This makes the process more complex and increases risk of contamination. The dipeptides
- cQrex® AQ (L-Alanyl-L-Glutamine)
- cQrex® GQ (Glycyl-L-Glutamine)
are chemically stable forms of L-glutamine which can be used to prepare storage stable basal media and feeds. These highly bioavailable peptides have a long and successful history across a range of cell culture applications. They are metabolized at different rates, which allows fine-tuning of the L-glutamine supply depending on the cell types and requirements.
Improving the solubility of L-Tyrosine in cell culture systems
L-tyrosine is an important amino acid for protein synthesis and cellular metabolism. However, it is poorly soluble in cell culture media and cannot be dissolved at the desired concentrations at neutral pH. While extreme pH values are often used to increase solubility, thIS process can face many drawbacks. To solve this challenge, Evonik has developed a selection of dipeptides to improve the solubility of L-tyrosine:
- cQrex® GY (Glycyl-L-Tyrosine)
- cQrex® AY (L-Alanyl-L-Tyrosine)
They increase the solubility at neutral pH by up to 50 times compared to free L-tyrosine. Full replacement of L-tyrosine is possible because these peptides are efficiently taken up and metabolized by the cell.
Better solubility for L-Cystine to enhance culture conditions
L-cysteine plays an important role in the protection of cells from oxidative stress because it is a building block for glutathione. However, it is highly reactive and readily forms dimeric L-cystine with low solubility in water, which will often precipitate in neutral pH feeds. Evonik has developed a solution to overcome those issues:
- cQrex® AC (N,N'-di-L-Alanyl-L-Cystine)
cQrex® AC is a highly soluble, stable and bioavailable form of L-cystine. As this peptide can be efficiently taken up as a source of L-cystine, it is ideal for increasing the concentration of L-cystine in basal media and for preparing highly concentrated feed and perfusion media.
Other cell culture solutions to further improve application performance
Using the cQrex® peptides to partially or fully replace amino acids in basal, feed and perfusion media helps to increase yields and generate more stable and robust processes. In addition to these peptides, Evonik also offers a range of ingredients which further help to enhance media processes and cell culture performance:
- cQrex® AKG (α-Ketoglutaric acid)
cQrex® AKG is a titer-enhancing additive that can improve energy supply and protect cells against oxidative damage.
- cQrex® Carnosine
This peptide can protect against oxidative stress and prevent or reverse senescence in primary and stem cell cultivation.
- PhytoChol® Biopharma
PhytoChol® Biopharma is an animal-origin free cholesterol that helps improve cell culture outcomes.
Specialty carbohydrates like D-Mannose can be used as alternative energy sources and building blocks for intracellular protein glycosylation.
Order a sample of cQrex® ingredients: chemically defined and non-animal derived
Evonik has combined its portfolio of peptides and the keto acid AKG into an integrated sample kit that allows you to test our finest cell culture ingredients in your own cell culture system.
Discover for yourself how cQrex® peptides can help to stabilize components, extend cell longevity, solubilize critical constituents, optimize the concentration of essential nutrients and increase productivity. Individual samples of standard amino acids can also be supplied upon request.