What makes a good new therapeutic l -asparaginase?

Abstractl-asparaginase is a critical part of the treatment of acute lymphoblastic leukaemia in children and adolescents, and has contributed to the improvement in patient outcomes over the last 40  years. The main products used in clinical treatment arel-asparaginase enzymes derived fromEscherichia coli andErwinia chrysanthemi. However, a very active area of research is the identification and characterisation of potential newl-asparaginase therapeutics, from existing or novel prokaryotic and eukaryotic sources, including mutations to improve function. In this review, we discuss the critical factors necessary to adequately characterise novell-asparaginase therapeutic products, including enzyme kinetic parameters, glutaminase activity, and toxicity. One critical consideration is to ensure that the substrate affinity of novel enzymes, as measured by the Michaelis constant KM, is sufficiently low to enable efficient reaction rates in human clinical use. The activity ofl-asparaginases towards glutamine as a substrate is discussed and reviewed in detail, as there is much debate in the scientific literature about the importance of this feature for therapeutic enzymes. The recent research in the area is reviewed, including identification of new sources of the enzyme, modulating glutaminase activity, and improving the thermal stability and immunogenic response. New research in the area may benefit from these considerations, to enable the next generation of therapeutic product design....
Source: World Journal of Microbiology and Biotechnology - Category: Microbiology Source Type: research