Organic & Biomolecular Chemistry Blog

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, Associate Editor Scott Silverman has highlighted some of his favourite recent works. Take a look at what they thought of the articles below, and find out more about the research and the researchers behind the papers in our interviews with the authors.

Scott’s Selection:

Post-synthetic transamination at position N4 of cytosine in oligonucleotides assembled with routinely used phosphoramidites

Rémy Lartia, Coelio Valléea and Eric Defrancq

Scott’s comments: Lartia et al. offer an elegant way to prepare site-specifically modified DNA oligonucleotides using standard and inexpensive reagents. This interesting approach is analogous to “convertible nucleotides” but takes advantage of the reactivity of the standard benzoyl-deoxycytidine (BzdC) monomer with various nucleophilic amines. The findings should be practically useful for investigators in several contexts, such as when wanting to prepare a series of sequence-related modified oligonucleotides without high cost.

Find out more in our interview with the authors

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

Catalina Cortés-Guajardo, Francisca Rojas-Hernández, Romina Paillao-Bustos and Marjorie Cepeda-Plaza

Scott’s comments: Cepeda-Plaza and coworkers nicely build on prior work by examining the role of a specific nucleobase in the catalytic activity of an RNA-cleaving DNAzyme. They distinguish two proton-transfer steps and find that a hydrated Mg²⁺ ion acts as a general acid to protonate the leaving group during the reaction. This mechanistic insight is valuable, especially given how little is known overall about DNAzyme mechanisms.

Find out more in our interview with the authors

Approaches for peptide and protein cyclisation

Heather C. Hayes, Louis Y. P. Luk and Yu-Hsuan Tsai

Scott’s comments: Peptide and protein cyclization is important process for both biology and chemistry. In this review, Luk and coworkers summarize various methods for cyclization that use chemical reagents, enzymes, and protein tags. Considering the broad importance of peptide and protein cyclization in many fields, this review should be useful for a variety of investigators as they plan their own experiments.

Find out more in our interview with the authors

Meet the Editor:

Scott Silverman, OBC Associate Editor

Scott K. Silverman was born in 1972 and raised in Los Angeles, California. He received his BS in chemistry from UCLA in 1991, working with Christopher Foote on photooxygenation mechanisms. He obtained his PhD in chemistry from Caltech in 1997, working with Dennis Dougherty to study high-spin organic polyradicals and molecular neurobiology. After postdoctoral research on RNA biochemistry with Thomas Cech at the University of Colorado at Boulder, he joined the University of Illinois in 2000, where he is currently Professor of Chemistry.

Professor Silverman’s research is in the chemistry and biochemistry of nucleic acids, especially investigations of DNA as an enzyme (DNAzyme, deoxyribozyme).

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

See every article in the full Editor’s Collection

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

See every article in the full Editor’s Collection