α-Chymotrypsin catalyses the synthesis of methotrexate oligomers

Noro, Jennifer; Castro, Tarsila G.; Cavaco‐Paulo, Artur; Silva, Carla

doi:10.1016/j.procbio.2020.08.004

Cited by 3 publications

(4 citation statements)

References 30 publications

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“…Noro et al used two different hydrolases for the modification of methotrexate (MTX). A protease (α-chymotrypsin from Bovine pancreas) [29] and two lipases (from C. antarctica B and Thermomyces lanuginosus [TL]). [24] MTX is a pharmaceutical drug, available in the market, with many therapeutical applications.…”

Section: Pharmaceutical Applicationsmentioning

confidence: 99%

Chemical modification of lipases: A powerful tool for activity improvement

Noro

Cavaco‐Paulo

Silva

2022

Biotechnology Journal

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The demand for adequate and ecologically acceptable procedures to produce the most differentiated products has been growing in recent decades, with enzymes being excellent examples of the advances achieved so far. Lipases are astonishing catalysts with a vast range of applications including the synthesis of esters, flavors, biodiesel, and polymers. The broad specificity of the substrates, as well as the regio-, stereo-, and enantioselectivity, are the differentiating factors of these enzymes. Structural modification is a current approach to enhance the activity of lipases. Chemical modification of lipases to improve catalytic performance is of great interest considering the increasingly broad fields of application. Together with the physical immobilization onto solid supports, different strategies have been developed to produce catalysts with higher activity and stability. In this review, practical insights into the different strategies developed in recent years regarding the modification of lipases are described. For the first time, the impact of the modifications on the activity and stability of lipases, as well as on the biotechnological applications, is fully compiled.

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Section: Pharmaceutical Applicationsmentioning

confidence: 99%

Chemical modification of lipases: A powerful tool for activity improvement

Noro

Cavaco‐Paulo

Silva

2022

Biotechnology Journal

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“…The enzymatic synthesis of methotrexate (MTX) catalyzed by α-chymotrypsin was studied for the first time. The proteolytic enzyme displayed activity for the synthesis of MTX oligomers composed of six repeating units (DP avg = 1.5) [ 197 ]. The oligomerization of this drug would represent an alternative route for the treatment of many diseases by reducing some side effects associated with the monomer administration.…”

Section: Enzymes and Polymers Produced With Themmentioning

confidence: 99%

Prospects of Using Biocatalysis for the Synthesis and Modification of Polymers

Nikulin

Švedas

2021

Molecules

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Trends in the dynamically developing application of biocatalysis for the synthesis and modification of polymers over the past 5 years are considered, with an emphasis on the production of biodegradable, biocompatible and functional polymeric materials oriented to medical applications. The possibilities of using enzymes not only as catalysts for polymerization but also for the preparation of monomers for polymerization or oligomers for block copolymerization are considered. Special attention is paid to the prospects and existing limitations of biocatalytic production of new synthetic biopolymers based on natural compounds and monomers from biomass, which can lead to a huge variety of functional biomaterials. The existing experience and perspectives for the integration of bio- and chemocatalysis in this area are discussed.

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“…As recently noted by Noro and co‐workers, the in vivo stability of amide‐linked prodrugs relies on their hydrolysis by carboxylesterases, [11] peptidases, or proteases [12] . For example, proteases are enzymes that are commonly used to hydrolyze amide bonds between two amino acids [13] …”

Section: Introductionmentioning

confidence: 99%

“…[12] For example, proteases are enzymes that are commonly used to hydrolyze amide bonds between two amino acids. [13] Anhydride-containing copolymers have a wide range of uses for specific applications, notably as water solubility enhancers, starting materials for the formation of nanoparticles, surface chemical modification capabilities, synthetic macromolecular carrier system capacities, dental implants, and are effective agents in medical/diagnostic imaging. [14] Their current formulations in the field of biomedical application can be listed as polymer-based conjugates, micelles, nanoparticles, nanocapsules, nanogels, liposomes and dendrimers.…”

Section: Introductionmentioning

confidence: 99%

Decoration, Characterization and Antimicrobial Activity Evaluation of Novel Nano‐Based 1,2‐Phenylenediamine Functionalized Maleic Anhydride‐Allylphenyl Ether Conjugate

Karakus,

Atas

2023

ChemistrySelect

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Abstract1,2‐Phenylenediamine (o‐PDA) is a well‐known fluorescent dye that enables the decoration of next‐generation chemotherapeutics. A novel o‐PDA‐functionalized maleic anhydride‐allyl phenyl ether (poly(MA‐alt‐APE)/o‐PDA conjugate) was successfully synthesized according to the Ringsdorf model, which is the starting point for macromolecular prodrugs. Functional polymeric‐carriers were prepared by free‐radical polymerization in butyl acetate with azobisisobutyronitrile (AIBN) radical‐initiator at 70 °C. The conjugation was carried out at 40 °C in N,N‐dimethylformamide (DMF) using triethylamine (Et3N) as the conjugation catalyst. Characterization was performed by Attenuated Total Reflectance‐Fourier Transform Infrared (ATR‐FTIR), Nuclear Magnetic Resonance (1H‐NMR), UV‐Vis and Fluorescence Spectroscopy. Weight average molecular weight (Mw), number average molecular weight (Mn) and polydispersity index (PDI) (Mw/Mn) were calculated using gel permeation chromatography (GPC). The surface morphology was also elucidated by Transmission Electron Microscopy (TEM). Evaluation of antimicrobial activity against two Gram‐positive bacteria (Staphylococcus aureus, Bacillus cereus), two Gram‐negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and one yeast Candida albicans was performed using the broth microdilution method according to Clinical Laboratory Standards Institute (CLSI) criteria. Interestingly, S. aureus was found to be more sensitive to polymer‐based samples and, in particular, the minimum inhibitory concentration (MIC) of the conjugate was lower than that of ciprofloxacin used as a control compound.

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α-Chymotrypsin catalyses the synthesis of methotrexate oligomers

Cited by 3 publications

References 30 publications

Chemical modification of lipases: A powerful tool for activity improvement

Chemical modification of lipases: A powerful tool for activity improvement

Prospects of Using Biocatalysis for the Synthesis and Modification of Polymers

Decoration, Characterization and Antimicrobial Activity Evaluation of Novel Nano‐Based 1,2‐Phenylenediamine Functionalized Maleic Anhydride‐Allylphenyl Ether Conjugate

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