Immobilized Enzymes for Therapeutic Applications and for Large-Scale Production of Biologically Active Compounds

Author(s):  
Ichiro Chibata ◽  
Tetsuya Tosa ◽  
Takao Mori
2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Patrycja Redkiewicz ◽  
Agnieszka Sirko ◽  
Katarzyna Anna Kamel ◽  
Anna Góra-Sochacka

Many examples of a successful application of plant-based expression systems for production of biologically active recombinant proteins exist in the literature. These systems can function as inexpensive platforms for the large scale production of recombinant pharmaceuticals or subunit vaccines. Hemagglutinin (HA) is a major surface antigen of the influenza virus, thus it is in the centre of interests of various subunit vaccine engineering programs. Large scale production of recombinant HA in traditional expression systems, such as mammalian or insect cells, besides other limitations, is expensive and time-consuming. These difficulties stimulate an ever-increasing interest in plant-based production of this recombinant protein. Over the last few years many successful cases of HA production in plants, using both transient and stable expression systems have been reported. Various forms of recombinant HA, including monomers, trimers, virus like particles (VLPs) or chimeric proteins containing its fusion with other polypeptides were obtained and shown to maintain a proper antigenicity. Immunizations of animals (mice, ferrets, rabbits or chickens) with some of these plant-derived hemagglutinin variants were performed, and their effectiveness in induction of immunological response and protection against lethal challenge with influenza virus demonstrated. Plant-produced recombinant subunit vaccines and plant-made VLPs were successfully tested in clinical trials (Phase I and II) that confirmed their tolerance and immunogenicity.


2020 ◽  
Vol 24 (17) ◽  
pp. 1999-2018
Author(s):  
Vitor F. Ferreira ◽  
Thais de B. da Silva ◽  
Fernanda P. Pauli ◽  
Patricia G. Ferreira ◽  
Luana da S. M. Forezi ◽  
...  

Molecular rearrangements are important tools to increase the molecular diversity of new bioactive compounds, especially in the class of heterocycles. This review deals specifically with a very famous and widely applicable rearrangement known as the Dimroth Rearrangement. Although it has originally been observed for 1,2,3-triazoles, its amplitude was greatly expanded to other heterocycles, as well as from laboratory to large scale production of drugs and intermediates. The reactions that were discussed in this review were selected with the aim of demonstrating the windows that may be open by the Dimroth's rearrangement, especially in what regards the development of new synthetic approaches toward biologically active compounds.


2009 ◽  
Vol 82 (3) ◽  
pp. 439-444 ◽  
Author(s):  
Xiaoping Wu ◽  
Haishan Tian ◽  
Yadong Huang ◽  
Sixian Wu ◽  
Xiaoju Liu ◽  
...  

2011 ◽  
Vol 7 ◽  
pp. 59-74 ◽  
Author(s):  
Carolin Fischer ◽  
Burkhard Koenig

N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.


1977 ◽  
Vol 10 (2) ◽  
pp. 113-135 ◽  
Author(s):  
Carl-Göran Hedén

To talk about enzyme engineering in a context of global problems might seem easy, because the subject is so dynamic and its ramifications so numerous. One might for instance talk about the industrial use of immobilized enzymes to achieve steroid transformations suitable for large-scale production of drugs reducing fertility, or one could describe the application of the same technique for chopping off side-chains of penicillin and other antibiotics as a first step in the production of new semisynthetic drugs, that certainly have a global impact. Or it would be tempting to review the potential of enzyme engineering for synthesizing physiologically active polypeptides that find use in husbandry or medicine.


2008 ◽  
Vol 63 (3-4) ◽  
pp. 284-288 ◽  
Author(s):  
Tae Won Goo ◽  
Eun Young Yun ◽  
Sung Wan Kim ◽  
Kwang Ho Choi ◽  
Seok Woo Kang ◽  
...  

The insect baculovirus expression vector system (BEVS) is useful for the production of biologically active recombinant proteins. However, the overexpression of foreign proteins in this system often results in misfolded proteins and the formation of protein aggregates. To overcome this limitation, we have developed a versatile baculovirus expression and secretion system using the Bombyx mori protein disulfide isomerase (bPDI) as a fusion partner. bPDI gene fusion improved the secretion and antibacterial activity of recombinant enbocin proteins. Thus, bPDI gene fusion is a useful addition to the BEVS for the large-scale production of bioactive recombinant proteins


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