Discovery of human-like L-asparaginases with potential clinical use by directed evolution.

ABSTRACT: L-asparaginase is a chemotherapy drug used to treat acute lymphoblastic leukemia (ALL). The main prerequisite for clinical efficacy of L-asparaginases is micromolar K_M for asparagine to allow for complete depletion of this amino acid in the blood. Since currently approved L-asparaginases are of bacterial origin, immunogenicity is a challenge, which would be mitigated by a human enzyme. However, all human L-asparaginases have millimolar K_M for asparagine. We recently identified the low K_M guinea pig L-asparaginase (gpASNase1). Because gpASNase1 and human L-asparaginase 1 (hASNase1) share ~70% amino-acid identity, we decided to humanize gpASNase1 by generating chimeras with hASNase1 through DNA shuffling. To identify low K_M chimeras we developed a

SUBMITTER: Rigouin C 

PROVIDER: S-EPMC5579231 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature