Pegaspargase

Pegaspargase is a conjugate of monomethoxypolyethylene glycol (mPEG) and L-asparaginase (L-asparagine amidohydrolase), an asparagine-specific enzyme that converts L-asparagine into aspartic acid and ammonia. Asparagine is an amino acid that is vital for cell survival. In humans, most normal tissues can produce asparagine through the action of asparagine synthetase. However, leukemia cells have low levels of this enzyme and depend on exogenous sources. Therefore, the use of pegaspargase results in leukemic cell death. Pegaspargase has the same mechanism of action as L-asparaginase derived from Escherichia coli, a previously developed enzyme used for the treatment of acute lymphoblastic leukemia (ALL). However, using L-asparaginase derived from Escherichia coli may cause hypersensitivity in some patients and require frequent administration. The pegylation of pegaspargase allows access to the enzyme's active sites while limiting reticuloendothelial system uptake and reducing immune detection, and it also increases the half-life of L-asparaginase. In February 1994, pegaspargase was approved by the FDA for the treatment of ALL in patients with hypersensitivity to native forms of L-asparaginase.