scholarly journals Multi-Enzymatic Cascade One-Pot Biosynthesis of 3′-Sialyllactose Using Engineered Escherichia coli

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3567
Author(s):  
Zhongkui Li ◽  
Zhijian Ni ◽  
Xiangsong Chen ◽  
Gang Wang ◽  
Jinyong Wu ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Low Cost ◽  
Cost Effective ◽  
Fold Increase ◽  
Lacz Gene ◽  
Divalent Metal Ions ◽  
One Pot ◽  
Acetylneuraminic Acid ◽  
Cofactor Recycling

Among the human milk oligosaccharides (HMOs), one of the most abundant oligosaccharides and has great benefits for human health is 3′-sialyllactose (3′-SL). Given its important physiological functions and the lack of cost-effective production processes, we constructed an in vitro multi-enzymatic cofactor recycling system for the biosynthesis of 3′-SL from a low-cost substrate. First, we constructed the biosynthetic pathway and increased the solubility of cytidine monophosphate kinase (CMK) with chaperones. We subsequently identified that β-galactosidase (lacZ) affects the yield of 3′-SL, and hence with the lacZ gene knocked out, a 3.3-fold increase in the production of 3′-SL was observed. Further, temperature, pH, polyphosphate concentration, and concentration of divalent metal ions for 3′-SL production were optimized. Finally, an efficient biotransformation system was established under the optimized conditions. The maximum production of 3′-SL reached 38.7 mM, and a molar yield of 97.1% from N-acetylneuraminic acid (NeuAc, sialic acid, SA) was obtained. The results demonstrate that the multi-enzymatic cascade biosynthetic pathway with cofactor regeneration holds promise as an industrial strategy for producing 3′-SL.

Development of Natural Bioactive Alkaloids: Anticancer perspective

2021 ◽  
Vol 21 ◽  
Author(s):  
Ashish Patel ◽  
Ravi Vanecha ◽  
Jay Patel ◽  
Divy Patel ◽  
Umang Shah ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Low Cost ◽  
Chemical Compounds ◽  
Cost Effective ◽  
Drug Discovery And Development ◽  
Anticancer Properties ◽  
Antimetastatic Activity ◽  
New Chemical Entities

: Cancer is a frightful disease that still poses a 'nightmare' worldwide, causing millions of casualties annually due to one of the human race's most significant healthcare challenges that requires a pragmatic treatment strategy. However, plants and plant-derived products revolutionize the field as they are quick, cleaner, eco-friendly, low-cost, effective, and less toxic than conventional treatment methods. Plants are repositories for new chemical entities and have a promising cancer research path, supplying 60% of the anticancer agents currently used. Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery and development. However, some alkaloids derived from natural herbs display anti-proliferation and antimetastatic activity on different forms of cancer, both in vitro and in vivo. Alkaloids have also been widely formulated as anticancer medications, such as camptothecin and vinblastine. Still, more research and clinical trials are required before final recommendations can be made on specific alkaloids. This review focuses on the naturally-derived bioactive alkaloids with prospective anticancer properties based on the information in the literature.

scholarly journals One-pot synthesis of a stable and cost-effective silver particle-free ink for inkjet-printed flexible electronics

2020 ◽  
Vol 8 (46) ◽  
pp. 16443-16451
Author(s):  
Wendong Yang ◽  
Florian Mathies ◽  
Eva L. Unger ◽  
Felix Hermerschmidt ◽  
Emil J. W. List-Kratochvil
Keyword(s):  
Flexible Electronics ◽  
Silver Particle ◽  
Low Cost ◽  
Cost Effective ◽  
Good Stability ◽  
Flexible Substrates ◽  
One Pot ◽  
One Pot Synthesis ◽  
Do It Yourself

A do-it-yourself silver particle-free ink is presented, which shows good stability, low cost and excellent printability. The ink is formulated in selected alcohols. Highly conductive silver patterns were printed on both glass and flexible substrates.

scholarly journals Building on Surface-Active Ionic Liquids for the Rescuing of the Antimalarial Drug Chloroquine

2020 ◽  
Vol 21 (15) ◽  
pp. 5334 ◽  
Author(s):  
Ana Teresa Silva ◽  
Lis Lobo ◽  
Isabel S. Oliveira ◽  
Joana Gomes ◽  
Cátia Teixeira ◽  
...  
Keyword(s):  
Ionic Liquids ◽  
Antimalarial Activity ◽  
Parent Drug ◽  
Cost Effective ◽  
Fold Increase ◽  
Pharmaceutical Ingredients ◽  
Ic50 Values ◽  
Surface Active ◽  
The Cost

Ionic liquids derived from classical antimalarials are emerging as a new approach towards the cost-effective rescuing of those drugs. Herein, we disclose novel surface-active ionic liquids derived from chloroquine and natural fatty acids whose antimalarial activity in vitro was found to be superior to that of the parent drug. The most potent ionic liquid was the laurate salt of chloroquine, which presented IC50 values of 4 and 110 nM against a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum, respectively, corresponding to an 11- and 6-fold increase in potency as compared to the reference chloroquine bisphosphate salt against the same strains. This unprecedented report opens new perspectives in both the fields of malaria chemotherapy and of surface-active ionic liquids derived from active pharmaceutical ingredients.

scholarly journals In Vivo Glycan Engineering via the Mannosidase I Inhibitor (Kifunensine) Improves Efficacy of Rituximab Manufactured in Nicotiana benthamiana Plants

2018 ◽  
Author(s):  
Vally Kommineni ◽  
Matthew Markert ◽  
Zhongjie Ren ◽  
Sreenath Palle ◽  
Berenice Carrillo ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Transient Expression ◽  
Nicotiana Benthamiana ◽  
Cost Effective ◽  
Fold Increase ◽  
Expression Platform ◽  
Dependent Cell ◽  
Anti Cd20

N-glycosylation has been shown to affect the pharmacokinetic properties of several classes of biologics including monoclonal antibodies, blood factors, and lysosomal enzymes. In the last two decades, N-glycan engineering has been employed to achieve a N-glycosylation profile that is either more consistent or aligned with a specific improved activity (i.e. effector function or serum half-life). In particular, attention has focused on engineering processes in vivo or in vitro to alter the structure of the N-glycosylation of the Fc region of anti-cancer monoclonal antibodies in order to increase antibody-dependent cell-mediated cytotoxicity (ADCC). Here we applied the mannosidase I inhibitor kifunensine to the Nicotiana benthamiana transient expression platform to produce an afucosylated anti-CD20 antibody (rituximab). We determined the optimal concentration of kifunensine used in the infiltration solution, 0.375 µM, which was sufficient to produce exclusively oligomannose glycoforms, at a concentration 14 times lower than previously published levels. The resulting afucosylated rituximab revealed a 14-fold increase in ADCC activity targeting the lymphoma cell line Wil2-S when compared with rituximab produced in the absence of kifunensine. When applied to the cost-effective and scalable N. benthamiana transient expression platform, the use of kifunensine allows simple in-process glycan engineering without the need for transgenic hosts.

A Green Alternative for Aryl Iodide Preparation from Aromatic Amines

2020 ◽  
Vol 17 (2) ◽  
pp. 131-135
Author(s):  
Zohreh Shahnavaz ◽  
Lia Zaharani ◽  
Mohd Rafie Johan ◽  
Nader Ghaffari Khaligh
Keyword(s):  
Low Cost ◽  
Cost Effective ◽  
Raw Material ◽  
Diazonium Salts ◽  
Separation And Purification ◽  
One Pot ◽  
Aryl Iodide ◽  
Aryl Iodides ◽  
The One

Background: In continuation of our previous work and the applications of saccharin, we encouraged to investigate the one-pot synthesis of the aryl iodides by the diazotization of the arene diazonium saccharin salts. Objective: Arene diazonium salts play an important role in organic synthesis as intermediate and a wide variety of aromatic compounds have been prepared using them. A serious drawback of arene diazonium salts is their instability in a dry state; therefore, they must be stored and handled carefully to avoid spontaneous explosion and other hazard events. Methods: The arene diazonium saccharin salts were prepared as active intermediates in situ through the reaction of various aryl amines with tert-butyl nitrite (TBN) in the presence of saccharin (Sac–H). Then, in situ obtained intermediates were used into the diazotization step without separation and purification in the current protocol. Results: A variety of aryl iodides were synthesized at a greener and low-cost method in the presence of TBN, Sac–H, glacial acetic acid, and TEAI. Conclusion: In summary, a telescopic reaction is developed for the synthesis of aryl iodides. The current methodology is safe, cost-effective, broad substrate scope, and metal-free. All used reagents are commercially available and inert to moisture and air. Also, the saccharine and tetraethylammonium cation could be partially recovered from the reaction residue, which reduces waste generation, energy consumption, raw material, and waste disposal costs.

scholarly journals Cytotoxicity and Sterilization Resistance of Electronic Components for Disposable Smart Biomedical Devices

2019 ◽  
Vol 5 (1) ◽  
pp. 297-301
Author(s):  
Valerie M. K. Werner ◽  
Daniel Strömsdörfer ◽  
Viet Nga Bui ◽  
Niklas von Wittenburg ◽  
Markus Eblenkamp
Keyword(s):  
Low Cost ◽  
Cost Effective ◽  
Electronic System ◽  
In Vitro Cytotoxicity ◽  
Future Research ◽  
Biomedical Devices ◽  
Electronic Components ◽  
Light Emitting ◽  
Standard Components

AbstractThe design of Smart Biomedical Devices will be a defining element of future research in the context of intelligent medical devices for the Internet of Medical Things (IoMT). A prerequisite for serving the disposable market is the use of cost-effective electronic components and the highest reliability of the developed products in terms of biocompatibility and bioprotection. In the study, resistors, capacitors, and light-emitting diodes, different in their materials and construction forms, were examined. The selected types represented electronic components as they are commonly installed on electronic system from the segment of low-cost standard components. These were subjected to steam sterilization with up to 50 cycles, gamma sterilization, and a CCK-8 assay to test in vitro cytotoxicity. Functional failure could not be determined for any component. Gamma sterilization did not result in significant changes in resistance values, but in capacitors with barium titanate as dielectric. Non-cytotoxic electronic components could be identified. The results show that certain electronic standard components are suitable for disposable Smart Biomedical Devices.

scholarly journals Multiplex Solid-Phase RPA Coupled CRISPR-Based Visual Detection of SARS-CoV-2

2021 ◽  
Author(s):  
Xiaochen Qin ◽  
Yuyuan Zhou ◽  
Ratul Paul ◽  
Yue Wu ◽  
Yaling Liu
Keyword(s):  
Solid Phase ◽  
Dna Detection ◽  
Point Of Care ◽  
Low Cost ◽  
Control Sample ◽  
Virus Detection ◽  
Cost Effective ◽  
Analytical Sensitivity ◽  
One Pot ◽  
Hpv Dna

COVID-19 has challenged the world's public health and led to over 4.5 million deaths. A rapid, sensitive, and cost-effective point-of-care virus detection device is crucial to the control and surveillance of the contagious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Here we demonstrate a solid phase isothermal recombinase polymerase amplification coupled CRISPR-based (spRPA-CRISPR) assay for on-chip multiplexed, sensitive, and visual COVID-19 DNA detection. By targeting the SARS-CoV-2 structure protein encoded genomes, two specific genes were simultaneously detected with the control sample without cross-interaction with other sequences. The endpoint signal can be directly visualized for rapid detection of COVID-19. The amplified target sequences were immobilized on the one-pot device surface and detected using the mixed Cas12a-crRNA collateral cleavage of reporter released fluorescent signal when specific genes were recognized. The system was tested with samples of a broad range of concentrations (20 to 2x105 copies) and showed analytical sensitivity down to 20 copies per reaction. Furthermore, a low-cost LED UV flashlight (~$12) was used to provide a visible SARS-CoV-2 detection signal of the spRPA-CRISPR assay which could be purchased online easily. Thus, our platform provides a sensitive and easy-to-read multiplexed gene detection method with the capacity to specifically identify low concentration genes. Similar CRISPR biosensor chips can support a broad range of applications such as HPV DNA detection, influenza SARS-CoV-2 multiplex detection, and other infectious disease testing assays.

scholarly journals Amberlite IR-120 Catalyzed Green and Efficient One-Pot Synthesis of Benzylpyrazolyl Coumarin in Aqueous Medium

2021 ◽  
Vol 10 (3) ◽  
pp. 2525-2534
Keyword(s):  
Reaction Time ◽  
Aqueous Medium ◽  
Ethyl Acetoacetate ◽  
Low Cost ◽  
Cost Effective ◽  
High Yield ◽  
Phenyl Hydrazine ◽  
One Pot ◽  
Time Operation ◽  
Effective Synthesis

An efficient, green, and cost-effective synthesis of benzylpyrazolyl coumarin by one-pot four-component condensation of hydrazine hydrate or phenyl hydrazine, ethyl acetoacetate, aromatic aldehyde, and 4-hydroxycoumarin in the presence of Amberlite IR-120 as a catalyst in an aqueous medium has been reported. Shorter reaction time, operation simplicity, low cost of catalyst, and aqueous medium are key advantages of this method for synthesizing benzylpyrazolyl coumarin in moderate to high yield.

Uniform iron oxide hollow spheres for high-performance delivery of insoluble anticancer drugs

2014 ◽  
Vol 43 (19) ◽  
pp. 7275-7281 ◽  
Author(s):  
Yichen Zhu ◽  
Jie Lei ◽  
Ye Tian
Keyword(s):  
Iron Oxide ◽  
Anticancer Drugs ◽  
High Performance ◽  
Hollow Spheres ◽  
Cost Effective ◽  
One Pot ◽  
Solvothermal Route

Novel magnetic hollow spheres based on iron oxide have been designed and synthesized via a facile and cost-effective one-pot solvothermal route, and have successfully acted as nanocarriers for the high-performance delivery of insoluble anticancer drugs in vitro.

scholarly journals In Vivo Glycan Engineering via the Mannosidase I Inhibitor (Kifunensine) Improves Efficacy of Rituximab Manufactured in Nicotiana benthamiana Plants

2019 ◽  
Vol 20 (1) ◽  
pp. 194 ◽  
Author(s):  
Vally Kommineni ◽  
Matthew Markert ◽  
Zhongjie Ren ◽  
Sreenath Palle ◽  
Berenice Carrillo ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Transient Expression ◽  
Nicotiana Benthamiana ◽  
Cost Effective ◽  
Fold Increase ◽  
Expression Platform ◽  
Dependent Cell ◽  
Anti Cd20

N-glycosylation has been shown to affect the pharmacokinetic properties of several classes of biologics, including monoclonal antibodies, blood factors, and lysosomal enzymes. In the last two decades, N-glycan engineering has been employed to achieve a N-glycosylation profile that is either more consistent or aligned with a specific improved activity (i.e., effector function or serum half-life). In particular, attention has focused on engineering processes in vivo or in vitro to alter the structure of the N-glycosylation of the Fc region of anti-cancer monoclonal antibodies in order to increase antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we applied the mannosidase I inhibitor kifunensine to the Nicotiana benthamiana transient expression platform to produce an afucosylated anti-CD20 antibody (rituximab). We determined the optimal concentration of kifunensine used in the infiltration solution, 0.375 µM, which was sufficient to produce exclusively oligomannose glycoforms, at a concentration 14 times lower than previously published levels. The resulting afucosylated rituximab revealed a 14-fold increase in ADCC activity targeting the lymphoma cell line Wil2-S when compared with rituximab produced in the absence of kifunensine. When applied to the cost-effective and scalable N. benthamiana transient expression platform, the use of kifunensine allows simple in-process glycan engineering without the need for transgenic hosts.

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