Increasing demands for protein‐based therapeutics such as monoclonal antibodies, fusion proteins, bispecific molecules, and antibody fragments require researchers to constantly find innovative solutions. To increase yields and decrease costs of next generation bioprocesses, highly concentrated cell culture media formulations are developed but often limited by the low solubility of amino acids such as tyrosine, cystine, leucine, and isoleucine, in particular at physiological pH. This study sought to investigate highly soluble and bioavailable derivatives of leucine and isoleucine that are applicable for fed‐batch processes. N‐lactoyl‐leucine and N‐lactoyl‐isoleucine sodium salts were tested in cell culture media and proved to be beneficial to increase the overall solubility of cell culture media formulations. These modified amino acids proved to be bioavailable for various Chinese hamster ovary (CHO) cells and were suitable for replacement of canonical amino acids in cell culture feeds. The quality of the final recombinant protein was studied in bioprocesses using the derivatives, and the mechanism of cleavage was investigated in CHO cells. Altogether, both N‐lactoyl amino acids represent an advantageous alternative to canonical amino acids to develop highly concentrated cell culture media formulations to support next generation bioprocesses.
Increasing demands for protein-based therapeutics such as monoclonal
antibodies, fusion proteins, bispecific molecules and antibody fragments
require researchers to constantly find innovative solutions. To increase
yields and decrease costs of next generation bioprocesses, highly
concentrated cell culture media formulations are developed but often
limited by the low solubility of amino acids such as tyrosine, cystine,
leucine and isoleucine, in particular at physiological pH. This work
sought to investigate highly soluble and bioavailable derivatives of
leucine and isoleucine that are applicable for fed-batch processes.
N-lactoyl-leucine and N-lactoyl-isoleucine sodium salts were tested in
cell culture media and proved to be beneficial to increase the overall
solubility of cell culture media formulations. These modified amino
acids proved to be bioavailable for various Chinese hamster ovary (CHO)
cells and were suitable for replacement of canonical amino acids in cell
culture feeds. The quality of the final recombinant protein was studied
in bioprocesses using the derivatives, and the mechanism of cleavage was
investigated in CHO cells. Altogether, both N-lactoyl amino acids
represent an advantageous alternative to canonical amino acids to
develop highly concentrated cell culture media formulations to support
next generation bioprocesses.
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