Using proteins in a therapeutic context often requires engineering to modify functionality and enhance efficacy. We have previously reported that the therapeutic antileukemic protein macromolecule Escherichia coli L-asparaginase is degraded by leukemic lysosomal cysteine proteases. In the present study, we successfully engineered L-asparaginase to resist proteolytic cleavage and at the same tim...

We analyzed the effect of asparagine starvation and L-asparaginase on RNA metabolism of mouse leukemia cell lines L5178Y, whose growth is dependent on the presence of asparagine, and L5178Y-R, whose growth is independent of the presence of asparagine. The deprivation of asparagine from the medium inhibited cellular protein synthesis by 30 to 40% of the control value in L5178Y cells, but not in ...

L-asparaginase (L-asparagine amido hydrolase, E.C.3.5.1.1) is an extra cellular enzyme that has received considerable attention since it is used as an anticancer agent. L-asparaginase belongs to an amidase group that hydrolyses the amide bond in Lasparagine to aspartic acid and ammonia. The clinical action of this enzyme as an anti-carcinogenic is attributed to the reduction of L-asparagine; tu...

The inactivation of E. coli asparaginase by 2,3-butanedione studied with L-asparagine and diazooxonorvaline as substrates obeys pseudo first order kinetics. Activity losses are linear with respect to arginine and histidine modification, with complete inactivation being correlated with alteration of one arginine and one histidine per subunit. The rate of inactivation of the enzyme was reduced in...

The physicochemical properties of the antileukemic Lasparaginase from Erwinia carotovora have been studied and compared with those of the corresponding clinically effective enzyme from Escherichia coli B. Although both enzymes are tetramers with similar molecular weight, the amino acid compositions are distinctly different and the Erwinia enzyme is more basic as judged by polyacrylamide electro...

Many side effects of current FDA-approved L-asparaginases have been related to their secondary L-glutaminase activity. The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutaminase free, suggesting it would have fewer side effects. Unexpectedly, the WoA variant with a proline at position 121 (WoA-P121) was found to have L-glutaminase activity in contrast to Uniprot entry...

The Oncologist 2005;10:238–239 www.TheOncologist.com Correspondence: David S. Goodsell, Ph.D., Associate Professor, The Scripps Research Institute, Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. Telephone: 858-784-2839; Fax: 858-784-2860; e-mail: [email protected] Website: http://www.scripps.edu/pub/goodsell Received January 5, 2005; accepted...

L-asparaginase is an anti-neoplastic agent used in the chemotherapy of lymphoblastic leukaemia. The present work deals with production of extra-cellular Lasparaginase from marine actinomycetes, using submerged fermentation. Marine actinomycete Streptomyces associated with marine spongeCallyspongia diffusa was isolated using specific ISP medium. Sponge-associated Streptomyces was character...

We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti-asparaginase antibody lev...

We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmacokinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti–asparaginase antibody leve...