Organic & Biomolecular Chemistry Blog

Marjorie Cepeda-Plaza

Francisca Rojas Hernández

Catalina Cortés Guajardo

Romina Paillao Bustos

Introducing the researchers:

Marjorie Cepeda-Plaza studied Chemistry at Universidad Chile and received her Doctorate in Chemistry from Pontificia Universidad Católica de Chile. After postdoctoral work with Dr. Yi Lu at the University of Illinois at Urbana Champaign, she joined the Chemical Science Department at Universidad Andrés Bello in Chile. Her research is focused on the study of the mechanisms of catalysis of DNAzymes. She is currently part of the Committee for Gender Equality in Research and the Academic Committee of the Center for the Communication of Science at the same University.

Francisca Rojas Hernández obtained her bachelor´s degree in Chemistry from Universidad Andrés Bello (UNAB) in 2020. Her thesis was focused on understanding the role of divalent metal ion in the catalytic mechanism of the 8-17 DNAzyme. She is currently working as a research assistant at the Laboratory of Bioinorganic Chemistry at UNAB. She also a great visual artist.

Catalina Cortés Guajardo obtained her master’s degree in Chemistry from Universidad de Chile in 2020. Her thesis was focused on fluorescent probes for singlet oxygen. She spent two years working as research assistant at the Laboratory of Bioinorganic Chemistry at UNAB. Now she is pursuing her doctorate degree on Chemistry at Universidad de Chile.

Romina Paillao Bustos is a biotechnologist from Universidad Mayor. She recently obtained her master’s degree in management and technological entrepreneurship from Universidad Adolfo Ibáñez. After spending six months doing research at the Laboratory of Bioinorganic Chemistry at UNAB she joined IQVIA working as CRA I.

What inspired your research in this area?

As a chemist, it was wonderful to discover the catalytic capabilities of DNA. What motivates my research is putting together the puzzle that relates DNA functional groups and conformations with their catalytic activity. Also, it is stimulating to be involved in the scientific formation of undergraduate students in Chile and relate them with the fascinating field of DNA catalysis.

What do you personally feel is the most interesting/important outcome of your study?

Our findings point out the stabilization of the 5′-O leaving group by the hydrated metal ion acting as a general acid in the phosphodiester transfer reaction catalyze by the 8-17 DNAzyme. These results are valuable to understand the precise role of divalent metal ion cofactors in the catalytic mechanisms of DNAzymes.

What directions are you planning to take with your research in future? What are you going to be working on next?

We continue working to understand the role of metal ions in the catalytic mechanism of the 8-17 DNAzyme. We are also trying to find out secondary and tertiary catalytic strategies that assist the RNA-cleavage reaction. In addition, we are interested in exploring similarities and differences among RNA-cleaving DNAzymes.

Read the full article: Hydrated metal ion as a general acid in the catalytic mechanism of the 8–17 DNAzyme

See the other articles showcased in this month’s Editor’s Collection

See every article in the full Editor’s Collection

Rémy Lartia

Eric Defrancq

Coélio Vallée

Introducing the researchers:

Rémy Lartia. After an engineer diploma and master degree (Univ. Rennes, France, 1998-2001), his Ph.D. research, under the supervision of Dr. Ulysse Asseline at CBM (Univ. Orléans, France,  2001-2004), focused on synthesis of fluorescent oligonuceotidic bioconjugates. In 2010, he joined the group of Prof. Marie-Paule Teulade-Fichou at the Collège de France (Paris, 2004-2006). During his two years of post-doctoral experience, he worked on synthesis of fluorescent triphenylamine derivatives.
He is currently research engineer on the Nanobio facility hosted by DCM (Univ. Grenoble, France, 2006) and works on peptide and oligonucleotides chemistry.

Eric Defrancq received his PhD (Organic Chemistry) in 1989 under the supervision of Prof. Jean Lhomme at the University Joseph Fourier of Grenoble. After two years of postdoctoral research with Prof. Tabacchi at the Institute of Chemistry at Neuchâtel (Switzerland), he returned to Grenoble in 1992 as an Assistant Professor, where he currently works as a full Professor.
His research interests lie in the field of modified oligonucleotide design for applications such as G-quadruplex and i-motif mimetics, aptamers as well as the design of photoreactive metal complexes for DNA targeting.

Coélio Vallée graduated from his Technician Diploma in General Chemistry in 2018 at the University of Montpellier. He joined the Nanobio facility in 2019 as technician on biomolecules synthesis where he performed the elaboration of peptides and oligonucleotides.

What inspired your research in this area?

Current trends in research mainly focus on more and more sophisticated reagents and/or investigation methods. Oppositely, it was thrilling to find out that very standard reagents can afford complex biomolecules such as orthogonally modified nucleic acids.

What do you personally feel is the most interesting outcome of your study?

For bioconjugates design, fine tuning of some parameters (notably tether length between the oligonucleotide and the reporter group) can afford dramatic change of the properties of the whole molecule. However, these parameters are rarely investigated as it often involves tedious multistep synthesis. Our method could easily overcome this difficulty. In the same context, another important outcome is that our method is relatively cheap in comparison with the others thus allowing the aforementioned investigations.

What directions are you planning to take with your research in future?

One direction is to use this method for the preparation of oligonucleotides bearing the cyclopropylamine reporter for photochemical purpose (it was the original need) because the previously described method required the use of very expensive phosphoramidite derivative.
Also, we are open to any collaboration with colleagues who are interested to obtain oligonucleotide conjugates.

Read the full article: Post-synthetic transamination at position N4 of cytosine in oligonucleotides assembled with routinely used phosphoramidites

See the other articles showcased in this month’s Editor’s Collection

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Researchers: Louis Luk (Cardiff Univeristy, School of Chemistry Lecturer) , Yu-Hsuan Tsai (Shenzhen Bay Laboratory) & Heather Hayes (Cardiff University PhD student)

What inspired you to write this Review article?

We are interested in the biophysical effects of polypeptide cyclisation. Considering the benefits cyclisation can confer (e.g. enhanced stability and activity), we wonder why it is not observed more often in nature. While there is a wealth of cyclisation methods to choose from, the suitability of particular techniques towards specific applications is infrequently discussed. Hence, we wanted to organise our thoughts by summarising the current state-of-the-art in this field.

What primary research are you carrying out in the area?

We have been preparing cyclised biocatalysts with the aim of improving their thermostability and solvent tolerance.

What are your thoughts on the future of this research field?

We believe negative results should also be published. Though it seems less exciting, the scientific community should know that the effect of cyclisation is case-dependent and does not necessarily improve the stability of a protein. By collecting sufficient data (both positive and negative), we may be able to apply AI and deep learning to better predict and design experiments.

Read the full article: Approaches for peptide and protein cyclisation

See the other articles showcased in this month’s Editor’s Collection

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Authors : (From left to right) Dr. Ya-Zhou Liu, Dr. Xiao Mu, Dr. Chieh-Kai Chan, Dr. Koen Robeyns, Dr. Cheng-Chung Wang, Dr. Michael Singleton

Introducing the researchers:

Dr. Ya-Zhou Liu was born in Linyi, China. He received his MSc degree from Guizhou University in 2015 under the supervision of Prof. Weidong Pan. He then joined the Université Catholique de Louvain for his PhD degree under the supervision of Prof. Istvan E. Marko on the development of indole chalcones for non-apoptotic cancer cell death. In 2017, he joined Prof. Michael L. Singleton’s group to continue his PhD research under the topic of using non-covalent interactions to control fluxional molecules into ordered conformations. After receiving his PhD degree in 2020, he joined the Chengdu Institute of Biology (CIB), Chinese Academy of Sciences as an assistant research fellow with Prof. Xiaofeng Ma, working on the development of enzyme-mimetic catalysts.

Dr. Xiao Mu was born in Zibo, China. She received her MSc degree from Zhejiang Normal University in 2015. In 2016, she arrived in Belgium and started her doctoral studies sponsored by the China Scholarship Council under the supervision of Prof. Michael Singleton on the topic of histidine brace-containing ligand scaffolds for developing biomimetics of lytic polysaccharide monooxygenases. She received her PhD degree in 2020.

Dr. Chieh-Kai Chan received his B.S. from the Department of Medicinal and Applied Chemistry, Kaohsiung Medical University in 2012. He later obtained his M.S. in 2014 and PhD in 2017 in the same department under the supervision of Prof. Meng-Yang Chang . He has been performing his postdoctoral studies with Prof. Cheng-Chung Wang in the Institute of Chemistry at Academia Sinica since 2017, and was awarded the Postdoctoral Scholar Program from Academia Sinica in 2018 and 2020. His current research interests are carbohydrate chemistry, the development of methodologies on small molecules and their applications on drug screening.

Dr. Koen Robeyns was born in Flanders, Belgium. He started undergraduate studies in chemistry at the KULeuven, Kortrijk, and completed his graduate studies at the KULeuven, Leuven, where he was first introduced to crystallography. He began his PhD studies in 2002 on the structural determination of modified DNA sequences, which he defended in 2006. After some years of postdoctoral research, combining both small-molecule and macromolecular crystallography, he moved to the UCLouvain, where he now works as permanent researcher in charge of single crystal studies.

Dr. Cheng-Chung Wang is an Associate Research Fellow at the Institute of Chemistry, Academia Sinica, Taiwan. He received his Ph.D. from TIGP, Academia Sinica under the supervision of Prof. Shang-Cheng Hung in 2008. He joined Prof. Peter H. Seeberger’s laboratory for his postdoctoral research at ETH, Switzerland, in 2008, and then moved to the Max-Planck-Institute of Colloids and Interfaces with Prof. Seeberger in 2009. He started his independent career in 2010, and his group in Academia Sinica is currently focusing on stereoselective glycosylation reactions, the synthesis of complex carbohydrate molecules and facile preparations of small molecules.

Dr. Michael Singleton received his PhD in 2010 from Texas A&M University under the supervision of Prof. Marcetta Darensbourg. He then moved to Bordeaux, France, where he worked as a Marie Curie Postdoctoral Fellow at the European Institute for Chemistry and Biology, working with Prof. Ivan Huc. In 2014, he started his independent career in the Institute of Condensed Matter and Nanoscience at the Université Catholique de Louvain in Belgium. His group’s research focuses on the synthesis and structural control of self-organized/self-assembled molecular architectures for mimicking the reactivity of biological molecules.

What inspired your research in this area?

Large-scale conformational changes in certain proteins can lead to switching of their function or self-assembly properties. Mimicking this process with synthetic oligomers can be used to control self-assembly, permit exchange between larger self-assembled structures, or to change interactions with small molecules.  The current work stems from this idea and our interest in understanding factors that can influence the stability of different folded states.

What do you personally feel is the most interesting/important outcome of your study?

The fluxional character of aromatic oligoamides is not only important as it relates to the stability of their structures, but also to their applications in molecular recognition and catalysis. As numerous members of this type of foldamer have been shown to bind discrete water molecules in the solid state and/or solution, this study highlights the influence this binding can have on the fluxional properties of the oligomer.

What directions are you planning to take with your research in future? What are you going to be working on next?

In the near future, the next steps will be finding conditions or sequences that allow stabilizing or switching to other conformations, for example helices or double helices. Ultimately, it will be interesting to use this conformational exchange to permit one aromatic oligoamide  sequence to perform multiple distinct functions, for instance, incorporating catalytic sites and switching between different catalytic reactions.

Read the full article: Water binding stabilizes stacked conformations of ferrocene containing sheet-like aromatic oligoamides

See the other articles showcased in this month’s Editor’s Collection

See every article in the full Editor’s Collection

Dr Alain Wagner and Dr Guilhem Chaubet

Introducing the researchers:

Dr Guilhem Chaubet is the co-director of the Biofunctional Chemistry team in Strasbourg. He joined the CNRS as an independent researcher in 2017 after a PhD at the University of Montpellier II (2010-2013) and a postdoctoral position at the University of Oxford (2014-2017). He investigates chemical conjugation of native proteins, focusing especially on the development of new strategies.

Dr Alain Wagner was born in Saint Avold, France in 1964.  After graduate studies at Strasbourg University under the supervision of Prof.Charles Mioskowski, he took up a postdoctoral fellowship at Affymax Research, Palo Alto, working under the supervision of Prof. Peter Schultz. He entered the CNRS in 1994. In 2001, he co-funded the company Novalix, now one of largest CROs in France. He returned to academic research in 2007 to start the biofunctional chemistry team. In 2014, he co-funded Syndivia, a start-up exploiting new bioconjugations and linker technologies in the field of ADC, and a few months ago, embarked on a new adventure of single cell secretion analysis by co-funding MicroOmiX. His current research focuses on studying chemical reactivity in complex biological systems with applications in drug delivery and droplet microfluidic-based single cell analysis.

What inspired your research in this area?

This work originated almost 10 years ago, when we started investigating in-vivo drug inactivation via strain-promoted azide-alkyne cycloaddition (SPAAC). We had selected an azide analogue of warfarin as our model drug and proved that its anticoagulant activity could be neutralized in mice after injection of a PEG-containing strained alkyne. While this work ended up being published a few years ago, it was during the course of its development that we noticed this odd behaviour of SPAAC being accelerated in human plasma compared to traditional solvent mixtures. Being puzzled by this observation, we decided to dig deeper, which ultimately led to this work published in OBC.

What do you personally feel is the most interesting/important outcome of your study?

I think it is the revision of classical synthetic chemistry rules when reactions are conducted in such a complex medium rather than in a flask, where you can precisely control the environment. Bioorganic chemistry thus challenges the way chemists think about and design their experiments, which fosters innovation and originality.

What directions are you planning to take with your research in future? What are you going to be working on next?

We keep working on new methodologies to access site-specific conjugation of native proteins, which ultimately could lead to protein-selective strategies and applications of these reactions in complex biological media.

Read the full article: Plasma induced acceleration and selectivity in strain-promoted azide–alkyne cycloadditions

See the other articles showcased in this month’s Editor’s Collection

See every article in the full Editor’s Collection

The Organic & Biomolecular Chemistry Editor’s collection is a showcase of some of the best articles published in the journal, hand selected by our Associate Editors and Editorial Board members. For this month’s selection, Judy I-Chia Wu has highlighted some of her favourite recent works. Take a look at what she thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Judy’s Selection:

Water binding stabilizes stacked conformations of ferrocene containing sheet-like aromatic oligoamides

Ya-Zhou Liu, Xiao Mu, Cheih-Kai Chan, Koen Robeyns, Cheng-Chung Wang and Michael L. Singleton

Judy’s comments: “Water binding is known to play an important role in stabilizing the structures of many biopolymers such as DNA, lignin, and protein structures. Here, Singleton and co-workers show that water binding also can be used to control fluxional movements of foldamers, highlighting an underappreciated aspect of conformation control in synthetic oligomers.”

Find out more in our interview with the authors

Plasma induced acceleration and selectivity in strain-promoted azide–alkyne cycloadditions

David Warther, Enes Dursun, Marion Recher, Sylvain Ursuegui, Michel Mosser, Joanna Sobska, Wojciech Krezel, Guilhem Chaubet and Alain Wagner

Judy’s comments: “Strain-promoted azide–alkyne cycloadditions (SPAAC) are an important class of bioorthogonal reactions, but kinetic studies of these reactions have been limited to solvents and mixtures that do not reflect the environment of in vivo systems. Here, Chaubet, Wagner and co-workers report the important effects of considering a complex medium, opening doors to studying in vivo applications of SPAAC reactions.”

Find out more in our interview with the authors

Recent advances in single-benzene-based fluorophores: physicochemical properties and applications

Jaehoon Kim, Ji Hyeon Oh and Dokyoung Kim

Judy’s comments: “Organic molecule-based fluorophores are opening a new era in biology and materials science. In this review, Kim and co-workers summarize advances in the development of single-benzene-based fluorophores (SBBFs) in the past 15 years. It continues to amaze me how small and simple molecules as such can have such broad applications in chemistry!”

Meet the Editor:

Judy I-Chia Wu, OBC Editorial Board Member

Judy is a physical organic chemist and currently an Assistant Professor at the University of Houston. She received her Ph.D. in 2011 from the University of Georgia under the supervision of Professor Paul Schleyer.

Her current research interests span topics in ground and excited-state aromaticity and antiaromaticity, photochemistry, supramolecular chemistry, and enzyme catalysis.