RSC Advances Blog

We are very pleased to introduce Jamie Antonio Portilla Salinas, corresponding author of the paper ‘Pyrazolo[1,5-a]pyrimidines-based fluorophores: a comprehensive theoretical-experimental study‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our October HOT articles. Jamie told us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and his article below and find more HOT articles in our online collection.

Meet the authors

Jaime Portilla studied for a degree and PhD at The Universidad del Valle located in Cali-Colombia, his birthplace. He carried out a PhD supervised by Jairo Quiroga on synthesis of 5-aminopyrazoles and their reaction with 1,3-bis-electrophilic compounds under eco-compatible strategies. After the award of his PhD in November 2007, he moved to Bogotá (January 2008) and was appointed as a lecturer in organic chemistry at The Universidad de los Andes. He was promoted to Associate Lecturer in 2011 and since August 2018 Jaime Portilla is ‘Associate Professor III’.

The Prof. Jaime Portilla group’s research (Bioorganic Compounds Research Group) focuses on eco-compatible organic synthesis strategies, with a particular interest in aza-heterocyclic compounds synthesis of biological and photophysical potential. (Source: ORCID.)

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Here we developed a new family of fluorescent molecules with interesting features such as easy to synthesize (and easily functionalizable) with excellent green chemistry performance, starting from low-cost raw materials and with outstanding photophysical properties in both solution and solid-state.

How big an impact could your results potentially have?
These results could be the beginning of the inclusion of sustainable parameters in the design of fluorescent probes for materials, chemosensors and/or biological applications.

Could you explain the motivation behind this study?
Recently, fluorescent compounds with biological activity have received attention due to the possibility of monitoring those compounds in biological media such as cells and biofluids. Our research group is working on designing new pharmacophores for cancer treatment based on pyrazolo[1,5-a]pyrimidines and we do believe that the incorporation of remarkable photophysical properties will be important for the study of key parameters such as the distribution of the biologically active compound inside the body and even at subcellular levels.

In your opinion, what are the key design considerations for your study?
From the optical properties for pyrazolo[1,5-a]pyrimidines described in our previous works, we decided to incorporate green chemistry principles due to needing sustainable research according to the United Nations Agenda 2030. Thus, these fluorophores well-known for their synthetic versatility and important biological properties were designed and obtained via a eco-friendly approach. In addition, the effect of a modulable donor groups at position 7 on the heterocyclic core was corroborated by computational calculations, which would contribute towards an intelligent design of ‘highly functional fluorophores’.

Which part of the work towards this paper proved to be most challenging?
The work most challenging was to find a good correlation of the experimental results with the theoretical calculations, since the optical phenomena are strongly governed by the microenvironment of the analyzed molecule.

What aspect of your work are you most excited about at the moment?
Here we identify compounds with excellent optical properties (QYSS up to 63%) emitting in the blue region, a color highly interesting in OLED’s research field. These results are remarkable and further research is ongoing in this direction.

What is the next step? What work is planned?
The results show us the possibility to functionalized the ring at position 4 (nitrogen atom) to generated pyrazolo[1,5-a]pyrimidine salts. At this moment we had found outstanding results in the field of anion detection using this approach. Once position 7 showed excellent results, we would like to explore the other positions on the core such as 2, 3 and 5. Also, the introduction of highly polar groups will improve the water solubility and exciting applications are expected from it. Some of these probes and related compounds will be tested in antitumor assays. And of course, to continue the study of some derivatives published here specifically in their device performance construction (OLED).

Pyrazolo[1,5-a]pyrimidines-based fluorophores: a comprehensive theoretical-experimental study
Alexis Tigreros, Sandra-L. Aranzazu, Nestor-F. Bravo, Jhon Zapata-Rivera and Jaime Portilla
RSC Adv., 2020,10, 39542-39552
DOI: 10.1039/D0RA07716J, Paper

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We are very pleased to introduce Dr Takuya Kitaoka, corresponding author of the paper ‘Nanocellulose enriches enantiomers in asymmetric aldol reactions‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our October HOT articles. Takuya told us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and his article below and find more HOT articles in our online collection.

Meet the authors

Dr Takuya Kitaoka is a professor at Kyushu University, Japan, who is in charge of Nanomaterials Chemistry and Sustainable Bioresources Science. He graduated from the University of Tokyo, Japan in 1993, and received his M.Sc. (Forest Products Science) in 1995 and his Ph.D. (Agricultural Science) in 2000, both from the University of Tokyo, Japan. Dr. Kitaoka is an expert in cellulose & paper chemistry. He has expanded his research into bioadaptive materials and interfacial organocatalysis inspired by inherent nanoarchitectures of nanocellulose. He was awarded “The Young Scientists’ Prize” from the Minister of Education, Culture, Sports, Science and Technology, Japan in 2007, “JSPS PRIZE” from the Japan Society for the Promotion of Science in 2011, “The Cellulose Society of Japan Award” from the Cellulose Society of Japan in 2013, and “Fiber Science and Technology Award” from the Society of Fiber Science and Technology, Japan in 2014.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Wood-derived nanofibers play a crucial role in regulating asymmetric catalysis to produce chiral products, which will expand the practical possibility of natural woody materials in state-of-the-art chemistry.

How big an impact could your results potentially have?
Inexpensive woody nanomaterials might gain equal performance to highly active rare metal catalysts.

Could you explain the motivation behind this study?
I believe that nano-organized natural polysaccharides have great potential for their nanostructure-triggered novel functions.

In your opinion, what are the key design considerations for your study?
The structural regularity of chiral sources on the surface of nanocellulose is the key to unlock the secret of nanocellulose in advanced materials applications.

Which part of the work towards this paper proved to be most challenging?
The combination of woody nanocellulose and proline, one of many natural amino acids, was a completely new challenge in asymmetric catalysis.

What aspect of your work are you most excited about at the moment?
Up until now, catalysts determine the product structures, but now wood does.

What is the next step? What work is planned?
I will expand the research and development opportunities of this novel metal-free organocatalytic system into other natural nano-polysaccharides, such as chitin and chitosan nanofibers, which will be applicable for a variety of valuable reactions in chemical industries.

Nanocellulose enriches enantiomers in asymmetric aldol reactions
Naliharifetra Jessica Ranaivoarimanana, Xin Habaki, Takuya Uto, Kyohei Kanomata, Toshifumi Yui and Takuya Kitaoka
RSC Adv., 2020,10, 37064-37071
DOI: 10.1039/D0RA07412H, Paper

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We are very pleased to introduce Professor Zoran Marković (University of Kragujevac), corresponding author of the paper ‘Several coumarin derivatives and their Pd(ii) complexes as potential inhibitors of the main protease of SARS-CoV-2, an in silico approach‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our September HOT articles. Zoran told us more about the work that went into this article and what he hopes to achieve in the future.

His article is also part of the coronavirus collection – all Royal Society of Chemistry articles on coronavirus research can be found here and are freely available until 1st January 2021. You can find more HOT articles in our online collection.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
In these challenging times of COVID-19 pandemics, it is of utmost interest to understand better the effects of various drugs on the virus and continue investigating new drugs. In our contribution, three molecules synthesized in our laboratory along with their Pd(II) complexes were theoretically analyzed as potential therapeutics and their effect compared to two already approved drugs, cinanserin, and chloroquine. This paper is of current interest because it allows scientists to obtain valuable data on structural parameters of molecules that could bind to the proteins of the virus and inhibit their action.

How big an impact could your results potentially have?
The theoretical predictions of the action of new therapeutics are an important step in any drug discovery as they save a significant amount of time and money. The impact of our research lies in the fact that coumarin derivatives, as naturally occurring compounds, and their palladium complexes were investigated for the first time as possible therapeutics and it was shown that they bind more tightly to the important protein of the virus than approved drugs. Special emphasis is put on the structural parameters governing stability which could lead to the prediction of structural features of new reactive drugs.

Could you explain the motivation behind this study?
The motivation for the research came from our current results on the synthesis of various coumarin derivatives and their transition metal complexes. The structures of obtained derivatives show similarities to those of approved drugs: the presence of chlorine atom, delocalized structure, two aromatic rings, etc. Therefore, we decided to perform a theoretical study using the novel docking and dynamics techniques on the recently solved structure of the SARS-CoV-2 M^pro protein and compare results to the approved drugs.

In your opinion, what are the key design considerations for your study?
The key considerations were the structural similarities between drugs and molecules obtained in our lab. After the results were obtained the special emphasis was put on the determination of intermolecular interactions that responsible for the binding of the molecules to the active position of the protein.

Which part of the work towards this paper proved to be most challenging?
The most challenging part was the analysis of the molecular interactions responsible for the difference in reactivity of approved drugs and our coumarin derivatives, as this required special attention to details and all of the amino acids of the active pocket.

What aspect of your work are you most excited about at the moment?
We are very excited that the molecules obtained in our laboratory show higher reactivity towards SARS-CoV-2 proteins, especially their metal complexes with Pd(II) which proved to be less toxic than other transition metals.

What is the next step? What work is planned?
The next step includes the development of the new synthetic routes for the coumarin derivatives that possess other structural moieties similar to the approved drugs and transition metal complexes with other non-toxic metals. This would be beneficial as structure-activity analysis would allow the extraction of new data for the structural features important for reactivity. Also, if the situation allows, the experimental research will commence to verify the results of theoretical studies.

Several coumarin derivatives and their Pd(ii) complexes as potential inhibitors of the main protease of SARS-CoV-2, an in silico approach
Dejan A. Milenković, Dušan S. Dimić, Edina H. Avdović and Zoran S. Marković
RSC Adv., 2020,10, 35099-35108
DOI: 10.1039/D0RA07062A, Paper

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We are very pleased to introduce Walter Rosas Arbelaez, first author of the paper ‘Hierarchical micro-/mesoporous zeolite microspheres prepared by colloidal assembly of zeolite nanoparticles‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our October HOT articles. Walter told us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and his article below and find more HOT articles in our online collection.

Meet the authors

Walter Rosas Arbelaez (1987) received his BSc degrees (2011) in Chemistry and Chemical Enginering from Universidad de Los Andes, Colombia. He completed his MSc degrees in Chemical Engineering (2013) at Universidad de Los Andes and in Polymer Science (2016 ) at Martin-Luther University Halle-Wittenberg, Germany. In 2016, he joined Prof. Palmqvist´s research group at Chalmers University of Technology, Sweden to continue his PhD studies in Materials Science focusing on synthesis and characterization of zeolitic materials and mesoporous carbons and the evaluation in different applications. He will be defending his PhD thesis in December 2020.

Walter Rosas Arbelaez and Professor Anders Palmqvist (Chalmers University of Technology)

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
The focus of the article was to develop a zeolite material with two different porosities (micro and meso) using silicalite-1 nanoparticles (ca. 100 nm) and aggregate them by a controlled evaporation process into well-defined micron-sized spheres. In addition, the process does not use any template to form mesopores but only by the interspace generated between the particles after their aggregation. We find this topic of high interest, since many similar materials have been prepared using mesopore templates and/or need long preparation times and high temperature, parameters that have a big impact in the production economics at large scale.

How big an impact could your results potentially have?
As mentioned above, the material prepared in this article does not need a mesoporogen (mesopore template) to generate the mesopores which has a big impact at the production cost. The properties of the materials can be tailored by varying certain synthesis and preparation conditions, offering the possibility to tailor materials based on the desired application. All of these can be prepared by having a method that has few hours of preparation at mild temperatures. Certainly, this will have an impact at the mass-production level .

Could you explain the motivation behind this study?
There are several mesoporous zeolites procedures out there with and without template. However, many of them do not show well interconnectivity of the porosities and have low surface areas, pore volumes and the product does not have a defined morphology and the costs for their production are considerably high.

In your opinion, what are the key design considerations for your study?
First of all, a stable water-in-oil emulsion is crucial, since it is in the water droplets where the assembly of the particles takes place. Further, the nanoparticle size and shape are critical parameters to prepare the material, since nanopartilces with well-defined morphologies are more sutibale for a controlled aggregation. The evaporation conditions such temperature and vacuum also tailor the final properties of the material. Some of this information was learned from a previous work in mesoporous silica microparticles done by our co-authors Andreas Fijneman and Dr Heiner Friedrich.

Which part of the work towards this paper proved to be most challenging?
The preparation of the colloidal zeolite sol was challenging, not from the synthesis perspective but from the post-treatment, since the pH of the colloidal sol seems to have an impact on the formation of the microspheres.

What aspect of your work are you most excited about at the moment?
We feel that our work has shown a new method that cannot be classified among the usual categories to prepare hierarchical zeolites and that through our method we can prepare mesoporous zeolite with well-defined morphology and good pore interconnectivity. Additionly it has one the highest pore volumes and surface areas reported for mesoporous zeolites made of similar zeolite structures. The method also enables the use of different zeolite particles both in size and nature and this can potentially generate multifunctional materials for applications in catalysis and separation. Last but not least, we see that our method is energy and cost efficient and can be implemented at the industrial level.

What is the next step? What work is planned?
The next step is to prepare mesoporous zeolites from different colloidal zeolites such as beta, TS-1 or ZSM-5 and measure their catalytic activity towards different reactive systems. Unfortunately, I will not take part on this, as in December, I will be defending my PhD thesis and in January I will join new projects, but hopefully some other members of my group will follow up.

Hierarchical micro-/mesoporous zeolite microspheres prepared by colloidal assembly of zeolite nanoparticles
Walter Rosas-Arbelaez, Andreas J. Fijneman, Heiner Friedrich and Anders E. C. Palmqvist
RSC Adv., 2020,10, 36459-36466
DOI: 10.1039/D0RA07394F, Paper

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We are very pleased to introduce Dr Mitsuru Ando, first author of the paper ‘Preparation of cationic proteoliposomes using cell-free membrane protein synthesis: the chaperoning effect of cationic liposomes‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our September HOT articles. Mitsuru told us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and his article below and find more HOT articles in our online collection.

Meet the authors

Dr Mitsuru Ando received his undergraduate degree in Polymer Science and Engineering in 2007 from Kyoto Institute of Technology by under the supervision of Professor Akira Murakami. He received his master degree and Ph.D. in Pharmaceutical Sciences from Kyoto University by under the supervision of Professor Yoshinobu Takakura in 2010 and 2013, respectively. After graduation, Dr. Ando has been a postdoctoral fellow at Graduate school of pharmaceutical sciences (2013-2014) and at the Department of Polymer Chemistry, Graduate school of Engineering, Kyoto University (2014-date). His research project focuses on membrane protein science, drug delivery system and synthetic biology.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Our article describes the investigation of the effect of cationic liposome, one of the drug delivery system scaffolds, on cell-free membrane protein synthesis and the preparation method of the bioactive membrane protein reconstituted cationic liposomes.

How big an impact could your results potentially have?
Our study provides the advanced drug delivery system based on combination of membrane protein-guide with cationic liposomes. This cationic proteoliposome has the potential of highly specific interaction with target ligand on plasma membrane and more efficient delivery of encapsulated liposomal content through improvements to cellular attachment, fusion and ultimately delivery.

Could you explain the motivation behind this study?
Since membrane proteins in modulating cellular homeostasis, they are expected for their use in advanced applications. However, compared with the soluble protein science, the membrane protein science is still quite preliminary. We hope to use membrane proteins as a membrane protein-conducted drug delivery targeting materials and biosensor chips.

In your opinion, what are the key design considerations for your study?
A key point for this study is to control the surface positive charge of liposome and the concentration of cationic lipids.

Which part of the work towards this paper proved to be most challenging?
The most challenging aspect is the optimization of cationic lipid contents and concentrations under cell-free protein synthesis to control droplet-like polyion complexes.

What aspect of your work are you most excited about at the moment?
At this moment, we are very excited in establishing the preparation method of cationic proteoliposomes to open the advanced drug delivery system pivoted membrane protein science.

What is the next step? What work is planned?
In the next step, we plan and performe to use other membrane protein-reconstituted cationic liposomes in the membrane protein-conducted drug delivery strategy.

Preparation of cationic proteoliposomes using cell-free membrane protein synthesis: the chaperoning effect of cationic liposomes
Mitsuru Ando, Yoshihiro Sasaki and Kazunari Akiyoshi
RSC Adv., 2020,10, 28741-28745
DOI: 10.1039/D0RA05825D, Paper

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We are very pleased to introduce Professor Hamdy M. Abdel-Rahman, Dr Asmaa M. AboulMagd and Mr Mostafa A. Mansour, the authors of the paper ‘Quinazoline-Schiff base conjugates: in silico study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins‘. Their article has been very well received and handpicked by our reviewers and handling editors as one of our September HOT articles. The authors told us more about the work that went into this article and what they hope to achieve in the future. You can find out more about the authors and their article below and find more HOT articles in our online collection.

Meet the authors

Prof. Hamdy M. Abdel-Rahman received the Ph.D. degree in medicinal chemistry in 1999 in a joint supervision system between Faculty of Pharmacy Assiut University, Egypt and Kyoto Pharmaceutical University, Japan. After Two postdoctoral positions, from 2002-2004, at Kyoto Pharmaceutical University, Japan and from 2006-2009 at institute of cancer therapeutics, Bradford University, UK; he returned back to Assiut University, Egypt where he promoted to full professor in 2012. From 2014 he joined the Faculty of Pharmacy, Nahda University, Egypt, where he is the dean from 2018 till now.

Dr. Asmaa M. AboulMagd received the Ph.D. degree in pharmaceutical chemistry in 2016 from Faculty of Pharmacy, Ain Shams University. She is interested in design and synthesis of small molecules with potential biological activities and the use of computer aided drug design. Since 2017, she has been a lecturer of pharmaceutical chemistry at Faculty of Pharmacy, Nahda University, Egypt, till now.

Mr. Mostafa A. Mansour graduated from Faculty of pharmacy, Nahda University, Egypt in 2013 and received the Master degree in medicinal chemistry in 2020 from Faculty of Pharmacy, Beni-Suef University, Egypt. Interested in computer aided drug design techniques.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
The focus of this article is to find a drug for treatment of coronavirus diseases COVID-19.

How big an impact could your results potentially have?
Reaching to a therapeutic drug against coronavirus will have a social, economic, and political impact.

Could you explain the motivation behind this study?
In a previous work, we have designed and synthesized a class of synthetic compounds and were evaluated against PDE 4B activity (anti-inflammatory in chest diseases), we thought that this would be ideal pharmaceutical therapy against COVID-19 disease.

In your opinion, what are the key design considerations for your study?
The key design considerations in this study is to find out that these compounds could be used as potential therapeutic agents for COVID-19.

Which part of the work towards this paper proved to be most challenging?
COVID-19 pandemic is considered as a global health crisis of our time and the greatest challenge we have faced nowadays.

What aspect of your work are you most excited about at the moment?
Using computer modeling softwares, we proved that these compounds have a potential therapeutic effect on coronavirus by several mechanisms.

What is the next step? What work is planned?
The in-vitro evaluation of the biological activity of the synthesized derivatives is our next step in an attempt to discover a potential multi-target agent against coronavirus.

Quinazoline-Schiff base conjugates: in silico study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins
Mostafa A. Mansour, Asmaa M. AboulMagd and Hamdy M. Abdel-Rahman
RSC Adv., 2020,10, 34033-34045
DOI: 10.1039/D0RA06424F, Paper

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We are very pleased to introduce Dr Shuntaro Takahashi and Professor Naoki Sugimoto, first author and corresponding author of the paper ‘Molecular crowding induces primer extension by RNA polymerase through base stacking beyond Watson–Crick rules‘. Their article has been very well received and handpicked by our reviewers and handling editors as one of our September HOT articles. The authors told us more about the work that went into this article and what they hope to achieve in the future. You can find out more about the authors and their article below and find more HOT articles in our online collection.

Meet the authors

Shuntaro Takahashi is an Associate Professor at the Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Japan. Dr. Takahashi earned his PhD degree at Tokyo Institute of Technology in 2007. After a period of research at Tokyo Institute of Technology as an Assistant Professor, he joined FIBER in 2012. He is currently studying the biophysics of nucleic acids in cells and the mechanism of molecular crowding for nucleic acid structures that affect cellular metabolism.

Professor Sugimoto received his PhD in 1985 from Kyoto University, Japan. After completing his postdoctoral work at the University of Rochester in the U.S.A., he became a faculty member at Konan University in Kobe, Japan in 1988. He has been a full professor since 1994 and a director at the Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University since 2003. He received The Imbach-Townsend Award from IS3NA in 2018. In 2020, he was awarded CSJ Awards from the Chemical Society of Japan. His research interests include biophysical chemistry, biomaterials, biofunctional chemistry, and biotechnology in the field of nucleic acid chemistry.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
We investigated the effect of chemical environments on gene replication of the virus RNA polymerase. This article provides insight into not only the evolution of life but also the mechanism of mutation of the virus genome including SARS-CoV-2.

How big an impact could your results potentially have?
Our results provide one story that the molecular environment could take part in the evolution of life by enhancing the replication error of genome sequences. Moreover, this study suggests the significance of molecular environments of patients’ cells for spreading viruses.

Could you explain the motivation behind this study?
The stability of the Watson-Crick base pair is NOT always the most stable, which can be perturbed by molecular environments. Therefore, we speculated that the replication of nucleic acids in the enzyme could also be affected by molecular environments and cause replication errors.

In your opinion, what are the key design considerations for your study?
The key design consideration of our study is to quantitatively understand the effect of molecular environments on the replication fidelity because the stability of nucleic acids structures depends on the physicochemical properties of the solution such as dielectric constant and water activity.

Which part of the work towards this paper proved to be most challenging?
For the reagents for the molecular environments, we used poly(ethylene glycol)s. Although these reagents were easy to tune the solution properties, the effect on RNA and protein were different and complex. The choice of suitable condition was very important for this kind of research.

What aspect of your work are you most excited about at the moment?
We were excited to find the replication rules became dependent on the stacking interactions more than Watson-Crick base pairing under molecular crowding conditions. This indicates that the replication error can be simply explained by the changes in dielectric constant.

What is the next step? What work is planned?
This study suggests that the rule of the base pairings can be differentiated under molecular crowding conditions. Thus, we will pursue the biological role of non-Watson-Crick base pairings such as Hoogsteen base pairs under different cellular conditions. We are also interested in the effect of molecular environments on the reaction of RNA-dependent RNA polymerase of Covid-19.

Molecular crowding induces primer extension by RNA polymerase through base stacking beyond Watson–Crick rules
Shuntaro Takahashi, Hiromichi Okura, Pallavi Chilka, Saptarshi Ghosh and Naoki Sugimoto
RSC Adv., 2020,10, 33052-33058
DOI: 10.1039/D0RA06502A, Paper

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We are very pleased to introduce He Dong, the corresponding author of the paper ‘Modular design and self-assembly of multidomain peptides towards cytocompatible supramolecular cell penetrating nanofibers‘. Her article has been very well received and handpicked by our reviewers and handling editors as one of our September HOT articles.  He Dong was kind enough to tell us more about the work that went into this article and what she hopes to achieve in the future. You can find out more about the author and their article below and find more HOT articles in our online collection.

Meet the Author

He Dong obtained her PhD degree in organic chemistry at Rice University in 2008. After postdoc work at Emory University and the University of California at Berkeley, she started her independent career in the Department of Chemistry and Biomolecular Science at Clarkson University in 2012. She joined the Department of Chemistry and Biochemistry at the University of Texas at Arlington in 2018. Her research is focused on biomimetic design and supramolecular assembly of soft matter nanomaterials for anticancer and antimicrobial therapy development. She received a NSF Faculty Early Career Award for her work on the design and self-assembly of antimicrobial peptides. Recently, she was named as an Emerging Investigator of Journal of Materials Chemistry for the development of stimuli-responsive cell penetrating nanomaterials.

Dong Group

Graduate students Weike Chen (1st from the left), Ryan Madigan (2nd from the Left), Su Yang (2nd from the right) and Dr. He Dong (1st from the right) at the UTA Science & Engineering Innovation & Research Building.

Project defense of a high school student, Sidney Wang (2nd from the left) who was selected for research experiences of 2019 Welch Summer Scholar Program. Sidney’s project is to study the fundamental physicochemical property of supramolecular peptide nanofibers. Sidney’s mother (1st from the left), undergraduate student, Samuel Gardner (1st from the right) and Dr. Dong (2nd from the right) attended her defense.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
The efficacy of chemotherapy or gene therapy, in large part, depends on the ability of chemotherapeutics or genetic materials to cross the cell membrane to reach the cytoplasm. Designing nanomaterials that can facilitate intracellular delivery of therapeutics to the cytosol is of great interests from both fundamental research and practical point of view. This work is focused on a supramolecular approach for the design, and synthesis of supramolecular cell penetrating nanofibers (SCPNs) which have potent membrane activity and excellent cytocompatibility for intracellular delivery of therapeutics and/or imaging agents.

How big an impact could your results potentially have?
The success of the project will substantially advance our ability to develop peptide-based cell penetrating nanomaterials for a range of biomedical applications which required the delivery of therapeutics inside the cell. The range of molecular and supramolecular chemistry developed in this project will lead to a comprehensive fundamental understanding of the structure-activity relationship beyond the molecular level. The acquired knowledge will help build up a solid foundation for the rational design of supramolecular nanostructured materials, in particular nanofiber-based materials for other applications, not limited to drug/gene delivery in the biological arena. They can be potential used for vaccine delivery and antimicrobial materials design and development, all of which require potent cell penetrating activity.

Could you explain the motivation behind this study?
The discovery of cell penetrating peptides (CPPs) has great impacts on both fundamental and translational biomedical research due to their seemingly at will ability to transverse the cell membrane. However, most natural and synthetic CPPs suffer from poor stability against proteolysis and rapid in vivo clearance. Peptide self-assembly offers an effective method to generate supramolecular nanomaterials with improved stability, dynamic nanostructure and biological activity. In particular, the high aspect ratio peptide nanofibers showed good in vivo stability and have been extensively studied as functional scaffolds and for a variety of in vivo biomedical applications. Inspired by both natural CPPs and fibrous peptides, we build a novel class of supramolecular cell penetrating nanofibers (SCPNs) through the self-assembly of integrated cationic -sheet forming peptides to overcome the intrinsic limitation of traditional CPPs while having potent cell penetrating activity and minimum cytotoxicity.

In your opinion, what are the key design considerations for your study?
The key design considerations are on the modular design and self-assembly of MDPs to afford supramolecular assemblies with tunable nanostructure morphology and cationic domain conformational flexibility. The combined supramolecular structures and conformational flexibility of the cationic domain play dual roles in mediating the cell penetrating activity and therefore drug delivery efficacy.

Which part of the work towards this paper proved to be most challenging?
Understanding the correlation between structure and cell penetrating activity requires detailed structural characterization on both the molecular and supramolecular level. The biggest challenges that we overcome is the elucidation of the solution self-assembly states adopted by different supramolecular assemblies and further their structure-dependent membrane activity.

What aspect of your work are you most excited about at the moment?
From the fundamental self-assembly point of view, the work is novel and significant as it established a general peptide self-assembly mechanism by which SPCNs can be generated and optimized for both nanostructures and cell penetrating activity. From a broader viewpoint of biomedical application, these MDPs can be readily modified with various chemical functionalities, particular those served as stimuli-responsive chemical linkers that can respond to a range of disease-specific microenvironment to turn on/off the cell penetrating activity. Such efforts would be greatly beneficial for the development of smart SPCNs as disease-specific molecular therapy and imaging agents.

What is the next step? What work is planned?
The current work laid solid foundation for the synthesis of tumor microenvironment (such as pH, enzymes, ROS or hypoxia) responsive SCPNs which have tumor-specific cell penetrating activity. These “smart” tumor-responsive SCPNs would be great candidates to test the in vivo stability, targeting efficacy and overall therapeutic efficacy of SCPNs.

Modular design and self-assembly of multidomain peptides towards cytocompatible supramolecular cell penetrating nanofibers
Su Yang and He Dong
RSC Adv., 2020,10, 29469-29474
DOI: 10.1039/D0RA04748A, Paper

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We are very pleased to introduce Rajendra Joshi and the team of authors of the paper ‘Remdesivir-bound and ligand-free simulations reveal the probable mechanism of inhibiting the RNA dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2‘. Their article has been very well received and handpicked by our reviewers and handling editors as one of our HOT articles. The team told us more about the work that went into this article and what they hope to achieve in the future. You can find out more about the authors and their article below and find more HOT articles in our online collection.

About Dr Rajendra Joshi

Dr. Rajendra Joshi received his Ph.D. in Biochemistry from National Chemical Laboratory, Pune, India in 1994. He has been associated with the area of Biotechnology & Bioinformatics for the about 28 years. He is presently serving as a Senior Director and Head of the Department, High Performance Computing-Medical and Bioinformatics Applications Group, at C-DAC, Pune.

His major area of expertise, is in the use of high performance parallel computers for biological research. His unique strength is in the form of good knowledge of biology and parallel computing. His main research interests include, molecular dynamics simulations of nucleic acids & proteins, genome sequence analysis, metabolic pathways and development of Problem Solving Environments. He has around 66 publications in internationally peer reviewed journals.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Remdesivir, the emergency drug approved for treating COVID-19 patients helps in blocking the multiplication of SARS-CoV-2 virus. The action of this drug on the viral protein RNA dependent RNA polymerase was mimicked using computational methods, namely, molecular docking and molecular dynamics simulations.

How big an impact could your results potentially have?
The predicted mechanism of action of the drug, remdesivir, on the viral protein of SARS-CoV-2 would help in designing inhibitor molecules against the viruses. The drug target protein is the one, which is observed to be the most conserved among the coronavirus family. Statistically significant results produced through computational drug repurposing methods, add to the prediction accuracy of the drug-target interactions that are of major interest to develop therapeutics.

Could you explain the motivation behind this study?
The need to find the best solution against the global pandemic was the biggest motivation behind this study. This work was performed in the month of May 2020 and during that time, remdesivir, was being considered as one of the best solutions to treat the COVID-19 patients until the designing of the vaccine. Understanding the mechanism adopted by remdesivir would add to the information on the drug-action mechanism. This would be of importance to the experimental and pharmaceutical labs in the process of drug development.

In your opinion, what are the key design considerations for your study?
The key design considerations of our study was to mimic the RNA dependent RNA polymerase inhibition by remdesivir. Trying to understand the structure of RdRP and designing the best fit molecule which can inhibit the drug target with more potency. Being a part of, one of the High Performance Computing (HPC) groups in India, the entire computational study was designed around making the best use of the HPC technologies available to us.

Which part of the work towards this paper proved to be most challenging?
The research work involved many challenges since we had to design simulation systems with limited and evolving structural information of this virus. The major challenge being performing the computational drug repurposing studies in order to accelerate this research. In addition, the analytics involving statistical techniques for the identification of crucial residues and subdomains of the viral protein RNA dependent RNA polymerase also proved to be challenging.

What aspect of your work are you most excited about at the moment?
The mechanism of action and crucial interacting residues predicted through the computational methods in our present study were observed to match the experimental structures that are being elucidated for the RNA dependent RNA polymerase of the SARS-CoV-2.

What is the next step? What work is planned?
The work in this article dealt with remdesivir action in inhibiting the RNA dependent RNA polymerase of SARS-CoV-2. Besides remdesivir, other nucleotide analogues are also known to inhibit RdRP from the other coronaviruses. Hence, we have planned to study the inhibitory mechanism of other nucleotide/nucleoside analogues namely, favipiravir, galidesivir, lamivudine, ribavirin and sofosbuvir in their active metabolite form. This work is currently being targeted using molecular docking and molecular dynamics simulations. We have planned to understand the conformational changes that the RdRP undergoes on binding to natural nucleotides and their analogues. This information may help in designing of better nucleotide analogues.

One more aspect we plan to study is the role of phytochemicals from medicinal plants that are known to be used as a treatment for respiratory ailments. All the data obtained through simulations has been thoroughly sampled and analyzed using statistically significant methods, such as, principal component analysis and Markov state modeling analysis.

Remdesivir-bound and ligand-free simulations reveal the probable mechanism of inhibiting the RNA dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2
Shruti Koulgi, Vinod Jani, Mallikarjunachari V. N. Uppuladinne, Uddhavesh Sonavane and Rajendra Joshi
RSC Adv., 2020,10, 26792-26803
DOI: 10.1039/D0RA04743K, Paper

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We are very pleased to introduce Marisa G. Santibáñez-Morán (first author), José Medina-Franco (corresponding author) and the team behind the paper ‘Consensus virtual screening of dark chemical matter and food chemicals uncover potential inhibitors of SARS-CoV-2 main protease‘. Their article has been very well received and handpicked by our reviewers and handling editors as one of our HOT articles. The team told us more about the work that went into this article and what they hope to achieve in the future. You can find out more about the authors and their research at DIFACQUIM, Computer-aided drug-design at UNAM, and find more HOT articles in our online collection.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Our article looks for molecules in food chemicals or dark chemical matter (molecules that had not shown activity in 100 or more high-throughput screening assays) that are prospective inhibitors of the SARS-CoV-2 Main protease.

How big an impact could your results potentially have?
It could point to SARS-CoV-2 inhibitors that might otherwise have been overlooked. We would be glad if other research groups will be interested in the computational hits we made publicly available and further analyzed them in experimental assays.

Could you explain the motivation behind this study?
COVID-19 is currently affecting all aspects of human life. Our research group works on computer-aided drug design, and we had previously worked on drug repurposing. We felt that we could and should contribute to the collaborative efforts of scientists from all around the world.

In your opinion, what are the key design considerations for your study?
One was the selection of the molecular libraries where we looked for potential inhibitors. These comprise compounds that recent studies on SARS-CoV-2 have analyzed on a limited basis. Additionally, a large number of these molecules are ready to be tested in experimental assays. Moreover, there are currently numerous papers that reported favorable molecular docking results. However, selecting compounds that would have satisfactory potency and biopharmaceutical results in experimental settings is not trivial. Therefore, we ranked the compounds considering positive results by two molecular docking programs, Machine learning predictions, commercial availability, and ADMETox properties.

Which part of the work towards this paper proved to be most challenging?
First, to select a target and molecular queries for the structural similarity analyses. The latter should include structurally diverse and promising compounds. Another challenge was to create a classification method that helps us select compounds with better possibilities for drug development.

What aspect of your work are you most excited about at the moment?
I am excited about the possibility of finding supporting information about the activity of food chemicals against SARS-CoV-2. I believe that this could result in the development of nutraceuticals with inhibitory activity against the SARS-CoV-2 virus.

What is the next step? What work is planned?
We are waiting for the experimental results of 3 compounds that are being tested by our collaborators in North Carolina. We are also working on another manuscript that explores a broader region of the chemical space. And we hope that we could form new collaborations with RSC Advances readers.

Consensus virtual screening of dark chemical matter and food chemicals uncover potential inhibitors of SARS-CoV-2 main protease
Marisa G. Santibáñez-Morán, Edgar López-López, Fernando D. Prieto-Martínez, Norberto Sánchez-Cruz and José L. Medina-Franco
RSC Adv., 2020,10, 25089-25099
DOI: 10.1039/D0RA04922K, Paper

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