ArticleScientific reports2017
A protease-resistant Escherichia coli asparaginase with outstanding stability and enhanced anti-leukaemic activity in vitro.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 66 citations in OpenAlex.
- Asparaginase with Combined Mutations: Optimized Biochemistry and Lowered Allergic Risk.ACS pharmacology & translational science · 2025Article
- Toward Safer Biotherapeutics: Expression and Characterization of a Humanized Chimeric L-Asparaginase inInternational journal of molecular sciences · 2025Article
- Reversible Substrate-Specific Photocontrol of the Chemotherapeutic Asparaginase(-Glutaminase) fromACS catalysis · 2025Article
- Differential effect of asparagine and glutamine removal on three adenocarcinoma cell lines.Heliyon · 2024Article
- Towards a dependable data set of structures for L-asparaginase research.Acta crystallographica. Section D, Structural biology · 2024Article
- The Improved Antineoplastic Activity of Thermophilic L-Asparaginase Tli10209 via Site-Directed Mutagenesis.Biomolecules · 2024Article
- Substrate Affinity Is Not Crucial for Therapeutic L-Asparaginases: Antileukemic Activity of Novel Bacterial Enzymes.Molecules (Basel, Switzerland) · 2024Article
- Desirable L-asparaginases for treating cancer and current research trends.Frontiers in microbiology · 2024Review
- Expression and Biological Evaluation of an Engineered Recombinant L-asparaginase Designed byAdvanced pharmaceutical bulletin · 2023Article
- The effects of nature-inspired amino acid substitutions on structural and biochemical properties of the E. coli L-asparaginase EcAIII.Protein science : a publication of the Protein Society · 2023Article
- Profiling Enzyme Activity of l-Asparaginase II by NMR-Based Methyl Fingerprinting at Natural Abundance.Journal of the American Chemical Society · 2023Article
- Asparagine and Glutamine Deprivation Alters Ionizing Radiation Response, Migration and Adhesion of a p53International journal of molecular sciences · 2023Article
- Possible mechanism of metabolic and drug resistance with L-asparaginase therapy in childhood leukaemia.Frontiers in oncology · 2023Review
- Hybrid Silica-Coated PLGA Nanoparticles for Enhanced Enzyme-Based Therapeutics.Pharmaceutics · 2022Article
- Massive annotation of bacterial L-asparaginases reveals their puzzling distribution and frequent gene transfer events.Scientific reports · 2022Article
- Microbial L-asparaginase as a promising enzyme for treatment of various cancers.Applied microbiology and biotechnology · 2022Review
- Structural and biophysical studies of new L-asparaginase variants: lessons from random mutagenesis of the prototypic Escherichia coli Ntn-amidohydrolase.Acta crystallographica. Section D, Structural biology · 2022Article
- Structural Aspects ofInternational journal of molecular sciences · 2022Article
- Molecular Analysis of L-Asparaginases for Clarification of the Mechanism of Action and Optimization of Pharmacological Functions.Pharmaceutics · 2022Review
- Novel Insights on the Use of L-Asparaginase as an Efficient and Safe Anti-Cancer Therapy.Cancers · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
L-Asparaginases (ASNases) have been used as first line drugs for paediatric Acute Lymphoblastic Leukaemia (ALL) treatment for more than 40 years. Both the Escherichia coli (EcAII) and Erwinia chrysanthemi (ErAII) type II ASNases currently used in the clinics are characterized by high in vivo instability, short half-life and the requirement of several administrations to obtain a pharmacologically active concentration. Moreover, they are sensitive to proteases (cathepsin B and asparagine endopeptidase) that are over-expressed by resistant leukaemia lymphoblasts, thereby impairing drug activity and pharmacokinetics. Herein, we present the biochemical, structural and in vitro antiproliferative characterization of a new EcAII variant, N24S. The mutant shows completely preserved asparaginase and glutaminase activities, long-term storage stability, improved thermal parameters, and outstanding resistance to proteases derived from leukaemia cells. Structural analysis demonstrates a modification in the hydrogen bond network related to residue 24, while Normal Mode-based geometric Simulation and Molecular Dynamics predict a general rigidification of the monomer as compared to wild-type. These improved features render N24S a potential alternative treatment to reduce the number of drug administrations in vivo and to successfully address one of the major current challenges of ALL treatment: spontaneous, protease-dependent and immunological inactivation of ASNase.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.