Cloning, expression and charactherization of L-asparaginases from Saccharomyces cerevisiae and comparison with bacterial L-asparaginases used to treat Leukemia.

• Grant number: 13/08139-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2013
• End date: December 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Gisele Monteiro
• Grantee: Mariana Silva Moreira Leite
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/01303-1 - Characterization of unknown function ORFs involved in Saccharomyces cerevisiae antioxidant response, AP.JP

Abstract

The L-asparaginase (ASPase) was discovered in the 1960s and it is used until the present day as a leading biopharmaceuticals to treat leukemia. It is an enzyme capable of catalyzing the cleavage of the amino acid asparagine (Asn) to form aspartic acid and ammonia. This prevents the uptake of extracellular Asn by tumor cells, causing decreased protein production and consequently decrease in DNA, and RNA levels, altering the cell cycle and inducing the apoptosis. Leukemic cells, unlike normal cells, possess little or no presence of asparagine synthetase, making them completely dependent upon the intake of this amino acid from extracellular media. The ASPases commercially available are of bacterial origin and they induce remission of acute lymphoblastic leukemia in children - ALL, and other. Currently, the greatest difficulty is the allergic reaction and the induction of an immune response caused by administration of a bacterial protein in humans. Furthermore, and perhaps more importantly, despite its importance in the treatment of leukemia juvenile, the overseas company supplying the product to Brazil discontinued the production of the ASPase. The ASPases obtained from the yeast S. cerevisiae, produced by genes ASP1 and ASP3 are still poorly studied and could be another option for antitumor therapy. This study aims to produce large quantities of the ASPases from S. cerevisiae and characterize their enzyme kinetics in comparison with the bacterial isoforms to assess whether they are possible to use for the treatment of ALL.

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

RODRIGUES, MARIANE A. D.; PIMENTA, MARCELA V.; COSTA, IRIS M.; ZENATTI, PRISCILA P.; MIGITA, NATACHA A.; YUNES, JOSE A.; RANGEL-YAGUI, CARLOTA O.; DE SA, MATHEUS M.; PESSOA, ADALBERTO; COSTA-SILVA, TALES A.; et al. Influence of lysosomal protease sensitivity in the immunogenicity of the antitumor biopharmaceutical asparaginase. Biochemical Pharmacology, v. 182, DEC 2020. (14/06863-3, 18/18257-1, 13/08617-7, 16/25896-5, 15/07749-2, 18/15104-0, 13/08139-8, 18/15549-1)