Author Archive

Meet the winners of the RSC Chemical Biology Outstanding Early Career Researcher Award 2023

We are thrilled to announce the launch of the prestigious Outstanding Early Career Research Award, aimed at recognising and celebrating outstanding contributions to RSC Chemical Biology. This initiative seeks to honour the dedication, innovation, and impactful research of promising early career researchers.

Benjamí Oller Salvia and his team are such remarkable individuals. In their paper, BrainBike peptidomimetic enables efficient transport of proteins across brain endothelium,  Prof Oller Salvia introduced BrainBikes, a novel family of bicyclic protease-resistant peptide shuttles designed to overcome the challenge of delivering protein therapeutics to the brain.

Protein therapeutics face a challenge in reaching the brain due to their low permeability across the blood-brain barrier (BBB). Despite previous attempts with brain shuttle peptides to enhance BBB transport of some therapeutics, effectively transporting protein cargoes remains difficult. In this study, the researchers introduce BrainBikes, a new family of bicyclic protease-resistant peptide shuttles capable of increasing transport of proteins, including antibody derivatives.

Using a trifunctional chemical linker, several bicyclic analogues are generated from a linear peptide targeting the transferrin receptor (TfR1). These analogues show increased metabolic resistance, with one variant, BrainBike-4 (BB4), demonstrating a high affinity for cells with high levels of TfR1. Initially, the researchers demonstrated that BB4 can enhance the transport of a model fluorescent protein by fourfold. Subsequently, BB4 is site-specifically conjugated to a single chain variable antibody fragment (scFv) using a chemoenzymatic approach. Conjugation of BB4 leads to a fivefold increase in the transport of the scFv in a human cell-based model of the BBB.

These results highlight the potential of bicyclic peptidomimetics as brain shuttles and present new opportunities for the transport of biotherapeutics across the BBB.

 

Meet the team

 

 

  • Maria C. Lucana pursued her undergraduate studies in Chemistry at Universitat Autònoma de Barcelona. Currently, she serves as a predoctoral researcher in Bioengineering at IQS – Ramon Llull University. Within the ChemSynBio group, Maria focuses on the development of shuttle peptides and nanocarriers aimed at enhancing therapeutic transport across the blood-brain barrier.
  • Roberta Lucchi’s academic journey began with Biotechnology studies at “La Sapienza” University in Rome. Following an enriching one-year internship at Nippon Kayaku Co. Ltd in Tokyo, funded by the “Vulcanus in Japan” program, she joined Dr Benjamí Oller-Salvia’s laboratory at IQS – Ramon Llull University. Here, she completed her PhD, focusing on the development of stimuli-responsive biotherapeutics, generously supported by an FPU scholarship from the Spanish Ministry of Science, Innovation, and Universities.
  • Fabien Gosselet, a distinguished figure in academia, holds the position of full professor at Université d’Artois. He received his PhD training at the Gustave Roussy Institute (IGR) and conducted postdoctoral research at the Blood-brain Barrier (BBB) laboratory (LBHE) in Lens. Since 2015, he has led the BBB Laboratory, delving into crucial areas such as the role of diet in amyloid clearance, relationships between cholesterol, BBB, and Alzheimer’s disease (AD), as well as exploring vectors for crossing the BBB
  • Cristina Díaz-Perlas brings a wealth of experience to the ChemSynBio group at IQS – Ramon Llull University as a Marie Curie postdoctoral researcher. Her academic journey includes PhD studies conducted in Prof Ernest Giralt’s laboratory at IRB Barcelona, followed by postdoctoral research at EPFL in Switzerland under the guidance of Prof Christian Heinis. In her current role, Cristina leads the research line on peptide and antibody phage display development, actively contributing to the discovery of efficient transport systems across the blood-brain barrier.
  • Benjamí Oller-Salvia is an associate professor at IQS – Ramon Llull University. He completed his PhD in Prof Ernest Giralt’s laboratory at IRB Barcelona, followed by postdoctoral research with Prof Jason Chin at the MRC LMB in Cambridge. Leading the ChemSynBio group at IQS, Benjamí combines chemical and synthetic biology to explore transport mechanisms across the blood-brain barrier. His research aims to generate smart biotherapeutics targeting brain diseases, generously supported by funding from the European Research Council.

About being awarded by the Editorial Board of RSC Chemical Biology, the winners commented: “We are immensely honoured and proud to receive this award. This prize is a recognition of the hard work and dedication of a wonderful research team that was the seed of the ChemSynBio group at IQS in Barcelona. This award motivates us to continue pushing the boundaries of the challenging field of brain delivery.”

As they continue to push the boundaries of scientific innovation, the possibilities for treating neurological disorders grow ever brighter. With each discovery, they edge closer to realizing their vision of a future where no disease is beyond the reach of effective treatment.

Join us on LinkedIn to celebrate Prof Oller Salvia and the team!

 

2023 RSC Chemical Biology Emerging Investigators collection

We’re pleased to announce that the second annual RSC Chemical Biology Emerging Investigators collection has now been published online!

 

READ THE COLLECTION 

 

 

This collection highlights the work of outstanding early career researchers from across the chemical biology community. We’ve provided links to just a few of these articles and the summary Profile below – be sure to visit the collection to read the rest!. All articles in RSC Chemical Biology are open access and free to read.

If you would like to nominate a colleague or yourself as an Emerging Investigator for our next collection, please contact us for further details. Emerging Investigators must be group leaders or principal investigators in the first 10 years of their independent career.

Profile

Contributors to the 2023 RSC Chemical Biology Emerging Investigators Collection

RSC. Chem. Biol., 2024, DOI: 10.1039/D4CB90013H


Communications

Biosynthesis of the fungal nonribosomal peptide penilumamide A and biochemical characterization of a pterin-specific adenylation domain

Stephanie C. Heard, Katharine L. Diehl and Jaclyn M. Winter

RSC. Chem. Biol., 2023, 4, 748–753, DOI: 10.1039/D3CB00088E

 

BrainBike peptidomimetic enables efficient transport of proteins across brain endothelium

Maria C. Lucana, Roberta Lucchi, Fabien Gosselet, Cristina Díaz-Perlas and Benjamí Oller-Salvia

RSC Chem. Biol., 2024, 5, 7–11, DOI: 10.1039/D3CB00194F


Papers 

Methylated guanosine and uridine modifications in S. cerevisiae mRNAs modulate translation elongation

Joshua D. Jones, Monika K. Franco, Tyler J. Smith, Laura R. Snyder, Anna G. Anders, Brandon T. Ruotolo, Robert T. Kennedy and Kristin S. Koutmou

RSC. Chem. Biol., 2023, 4, 363–378, DOI: 10.1039/D2CB00229A

 

Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking

Katerina Gavriel, Dustin C. A. van Doeselaar, Daniëlle W. T. Geers and Kevin Neumann

RSC. Chem. Biol., 2023, 4, 685–691, DOI: 10.1039/D3CB00062A


In addition to the researchers highlighted in our Profile article above, we’re pleased to feature this further contribution from Prof. Denise Okafor.

A portrait photograph of Denise Okafor

Denise Okafor is an assistant professor in the Departments of Biochemistry and Molecular Biology (BMB) and Chemistry at Pennsylvania State University. She received a B.S. in Biomedical chemistry from Oral Roberts University, followed by M.S. and Ph.D degrees in Chemistry from the Georgia Institute of Technology. As an NIH-IRACDA postdoctoral fellow at Emory University School of Medicine, she used molecular dynamics simulations to study ligand regulation and functional evolution in nuclear receptors. She began her independent career in 2020. Her lab combines MD simulations with biochemical experiments to understand mechanisms of transcriptional activation in nuclear receptors.

Read Prof. Okafor’s contribution below:

Ancient and modern mechanisms compete in progesterone receptor activation

RSC. Chem. Biol., 2024, 5,  DOI: 10.1039/D4CB00002A

New themed collection on ‘The Epitranscriptome’

From left to right Ralph Kleiner (Princeton University, USA), Claudia Höbartner (University of Würzburg, Germany) and Guifang Jia (Peking University, China)

 

 

We’re pleased to announce that a new themed collection from RSC Chemical Biology has now been published online.

 

Read the collection here

 

This themed collection, guest edited by Ralph Kleiner (Princeton University, USA), Claudia Höbartner (University of Würzburg, Germany) and Guifang Jia (Peking University, China), presents articles in the field of epitranscriptomics, delving into the exploration of non-canonical ribonucleotides in biology. Taken together, we hope that readers will find this small sampling of epitranscriptomic research, showcasing recent directions in the field, to be a stimulating and thought-provoking entry point for further reading and study.

The article line-up is shared below. We’re pleased to also feature a selection of epitranscriptomics articles published in RSC Chemical Biology before and after the collection was organised. All articles in RSC Chemical Biology are open access and free to read.


Editorial

Introduction to ‘The Epitranscriptome’

Ralph Kleiner, Claudia Höbartner and Guifang Jia

RSC. Chem. Biol., 2024, 5, DOI: 10.1039/D4CB90006E


Papers

Nucleoside analogs in ADAR guide strands targeting 5′-UA̲ sites

Hannah F. Brinkman, Victorio Jauregui Matos, Herra G. Mendoza, Erin E. Doherty and Peter A. Beal

RSC. Chem. Biol., 2023, 4, 74–83, DOI: 10.1039/D2CB00165A

 

Arabidopsis thaliana NudiXes have RNA-decapping activity

Maria-Bianca Mititelu, Oldřich Hudeček, Agnieszka Gozdek, Roberto Benoni, Ondřej Nešuta, Szymon Krasnodębski, Joanna Kufel and Hana Cahová

RSC. Chem. Biol., 2023, 4, 223–228, DOI: 10.1039/D2CB00213B

 

Temporal resolution of NAIL-MS of tRNA, rRNA and Poly-A RNA is overcome by actinomycin D

Authors

RSC. Chem. Biol., 2023, 4, 354–362, DOI: 10.1039/D2CB00243D

 

Advantages and challenges associated with bisulfite-assisted nanopore direct RNA sequencing for modifications

Aaron M. Fleming, Judy Zhu, Vilhelmina K. Done and Cynthia J. Burrows

RSC. Chem. Biol., 2023, 4, 952–964, DOI: 10.1039/D3CB00081H

 


Additional Papers

Methylated guanosine and uridine modifications in S. cerevisiae mRNAs modulate translation elongation

Joshua D. Jones, Monika K. Franco, Tyler J. Smith, Laura R. Snyder, Anna G. Anders, Brandon T. Ruotolo, Robert T. Kennedy and Kristin S. Koutmou

RSC. Chem. Biol., 2023, 4, 363–378, DOI:10.1039/D2CB00229A

 

N4-Allylcytidine: a new nucleoside analogue for RNA labelling and chemical sequencing

Tengwei Li, Xiao Shu, Minsong Gao, Chenyang Huang, Ting Li, Jie Cao, Xiner Ying, Donghong Liu and Jianzhao Liu

RSC. Chem. Biol., 2024, 5, DOI: 10.1039/D3CB00189J

 

Reversible oxidative dimerization of 4-thiouridines in tRNA isolates

Larissa Bessler, Jonathan Groß, Christopher J. Kampf, Till Opatz and Mark Helm

RSC. Chem. Biol., 2024, 5, DOI: 10.1039/D3CB00221G

 

We hope you enjoy this new themed collection from RSC Chemical Biology.

New themed collection on ‘Molecular Glues’

 

We’re pleased to announce that a new themed collection from RSC Chemical Biology has now been published online.

 

READ THE COLLECTION 

 

This themed collection, guest edited by Michelle Arkin (University of California San Francisco, USA), Luc Brunsveld (TU Eindhoven, Netherlands), and Eric Fischer (Dana-Farber Cancer Institute and Harvard Medical School, USA), encompasses the wide scope of molecular glues. Topics include protein degradation glues, protein binders and stabilizers, bi-functional molecules for protein degradation and beyond with a particular interest on molecular recognition.

The articles in this collection are listed below. All articles in RSC Chemical Biology are open access and free to read.

 

REVIEWS

Protein–protein interfaces in molecular glue-induced ternary complexes: classification, characterization, and prediction

Huan Rui, Kate S. Ashton, Jaeki Min, Connie Wang and Patrick Ryan Potts

RSC. Chem. Biol., 2023, 4, 192–215, DOI: 10.1039/D2CB00207H

 

Bringing enzymes to the proximity party

Gabrielle S. Tender and Carolyn R. Bertozzi

RSC. Chem. Biol., 2023, 4, 986–1002, DOI: 10.1039/D3CB00084B

 

PAPERS 

Accessing three-branched high-affinity cereblon ligands for molecular glue and protein degrader design

Robert Kuchta, Christopher Heim, Alexander Herrmann, Samuel Maiwald, Yuen Lam Dora Ng, Izidor Sosič, Tim Keuler, Jan Krönke, Michael Gütschow, Marcus D. Hartmann and Christian Steinebach

RSC. Chem. Biol., 2023, 4, 229–234, DOI: 10.1039/D2CB00223J

 

Straightforward model construction and analysis of multicomponent biomolecular systems in equilibrium

Nick H. J. Geertjens, Pim J. de Vink, Tim Wezeman, Albert J. Markvoort and Luc Brunsveld

RSC. Chem. Biol., 2023, 4, 252–260, DOI: 10.1039/D2CB00211F

 

A model-informed method to retrieve intrinsic from apparent cooperativity and project cellular target occupancy for ternary complex-forming compounds

Richard R. Stein, Marianne Fouché, Jeffrey D. Kearns and Hans-Joerg Roth

RSC. Chem. Biol., 2023, 4, 512–523, DOI: 10.1039/D2CB00216G

 

Bind&Bite: covalently stabilized heterodimeric coiled-coil peptides for the site-selective, cysteine-free chemical modification of proteins

Jannis Beutel, Pierre Tannig, Riccardo Di Vincenzo, Thomas Schumacher, Klaus Überla and Jutta Eichler

RSC. Chem. Biol., 2023, 4, 794–803, DOI: 10.1039/D3CB00122A

 

We hope you enjoy this new themed collection from RSC Chemical Biology.

Introducing Sander van Kasteren: Bridging Chemistry and Immunology as Associate Editor

Welcome to the team Sander!

Sander van Kasteren's picture

We’re excited to introduce Sander van Kasteren as our new Associate Editor. His ground-breaking work in chemistry and immunology brings a wealth of expertise and innovation to our editorial team.

Bridging Chemistry and Immunology

Sander’s research connects the dots between chemistry and immunology, focusing on understanding early immune reactions. His innovative methods for studying antigen presentation and T-cell activation are making waves in the scientific community.

Academic Journey

Starting as an organic chemistry student in Edinburgh, Sander’s journey led him to Oxford and the lab of Prof Benjamin G. Davis. There, he contributed to MRI and histological probes for detecting early brain inflammation. His expertise grew under Prof Colin Watts in Dundee, where he worked on protease inhibitors for better antigen cross-presentation.

Leadership and Recognition

In 2012, Sander founded his own group at Leiden University and later joined the Institute of Chemical Immunology, where he’s a board member. His remarkable contributions have earned him fellowships, grants, and awards, including the 2012 Early Career Investigator Award from the British Biochemical Society.

Associate Editor Role for RSC Chemical Biology

Now, Sander van Kasteren takes on a new role as our Associate Editor, bringing his expertise to our publication. We’re thrilled to welcome him and look forward to the valuable insights he’ll bring to our community.

 

 

RSC Chemical Biology is now indexed in the Directory of Open Access Journals (DOAJ), PubMed Central, Scopus and Web of Science: Emerging Sources Citation Index.  Find out more about the journal and submit your work at rsc.li/rsc-chembio

 

RSC Chemical Biology

Royal Society of Chemistry

www.rsc.org

 

 

Click’n lock: rapid exchange between unsymmetric tetrazines and thiols for reversible, chemoselective functionalisation of biomolecules with on-demand bioorthogonal locking

About this article:

Click reactions play a crucial role in efficiently modifying complex biomolecules, particularly in the realm of biotherapeutics. The continuous challenge lies in their reversible and irreversible transformations, with chemists seeking ultimate control over molecular structures in dilute conditions and crowded environments.

In this groundbreaking article, we introduce the Click’n Lock principle, describing a novel reaction system capable of seamlessly switching from reversible to irreversible click transformations. Termed ‘TeTEx’ for ‘tetrazine – thiol exchange,’ this concept enables on-demand locking of products using bioorthogonal stimuli (dienophiles), providing a transformative switch from reversible to irreversible attachment.

 

Ingo

 

About RSC Chemical Biology

Led by Hiroaki Suga (University of Tokyo), RSC Chemical Biology is dedicated to publishing and disseminating the most exceptionally significant, breakthrough findings of interest to the chemical biology community. All submissions are handled by our experienced and internationally recognised Associate Editors. For more information on the journal, please visit the journal homepage.

As a gold open access journal, there are no barriers to accessing content and your research article will reach an international audience. Please note that the article processing charges are waived until mid-2022, so the journal is currently free to publish in.

RSC Chemical Biology is now indexed in the Directory of Open Access Journals (DOAJ), PubMed Central, Scopus and Web of Science: Emerging Sources Citation Index.  Find out more about the journal and submit your work at rsc.li/rsc-chembio

 

RSC Chemical Biology

Royal Society of Chemistry

www.rsc.org

Predicting small molecule binding pockets on diacylglycerol kinases using chemoproteomics and AlphaFold

About this article

Explore the world of secondary messengers in cell signaling with our latest research on Diacylglycerol (DAG) lipids and their role in cellular communication. DAG kinases (DGK) control cellular DAG levels through phosphorylation, making them crucial in understanding cell signaling pathways. While small molecule inhibitors targeting DGK proteins are valuable tools for investigating DAG signaling, their development has been challenging due to limited information on binding pockets within cells.

Our ground-breaking approach combines chemical proteomics and AlphaFold technology to predict previously undiscovered binding regions for the development of covalent inhibitors.

 

Read the full article here.

 

 

About RSC Chemical Biology

Led by Hiroaki Suga (University of Tokyo), RSC Chemical Biology is dedicated to publishing and disseminating the most exceptionally significant, breakthrough findings of interest to the chemical biology community. All submissions are handled by our experienced and internationally recognised Associate Editors. For more information on the journal, please visit the journal homepage.

As a gold open access journal, there are no barriers to accessing content and your research article will reach an international audience. Please note that the article processing charges are waived until mid-2022, so the journal is currently free to publish in.

RSC Chemical Biology is now indexed in the Directory of Open Access Journals (DOAJ), PubMed Central, Scopus and Web of Science: Emerging Sources Citation Index.  Find out more about the journal and submit your work at rsc.li/rsc-chembio

 

RSC Chemical Biology

Royal Society of Chemistry

www.rsc.org

 

 

RSC Chemical Biology Webinar: Outstanding Paper Award Winner 2022

Join us to celebrate the Outstanding Paper Award winners of 2022!

The team at RSC Chemical Biology are delighted to invite you to our upcoming webinar to celebrate the winner of our Outstanding Paper Award from 2022. The winner is Professor Craig Crews, of Yale University, for their paper “OligoTRAFTACs: A generalizable method for transcription factor degradation”.

 

 

 

The webinar, scheduled to last for one hour, will feature a presentation from the group of Professor Craig Crews discussing their work, and this will be followed by a presentation from Professor Michelle Arkin, an Editorial Board Member for RSC Chemical Biology, highlighting some ongoing work in her group at the University of California, San Francisco.

This event is being held online through Zoom and is completely free to attend. It will be held on Tuesday 21st November at 17:00 GMT. You can find more information on our Event Page and can register for the event here.

We look forward to seeing you at the webinar!

 

 

The multivalent G-quadruplex (G4)-ligands MultiTASQs allow for versatile click chemistry-based investigations

About this article

G-quadruplexes (or G4s) are four-stranded DNA and RNA structures that fold from guanine (G)-rich sequences. G4 are suspected to play key biological roles in human cells and diseases. Small molecules that selectively target G4s (or G4-ligands) can thus be used as modulators to gain insights into the cell circuitry where G4s are involved. While hundreds of G4-ligands have been designed, synthesized and used, most if not all of them are flat aromatic molecules prone to interact with the duplex-DNA (the major form of DNA within the nucleus), which mechanically decreases their specificity for G4s.

We have developed a brand new molecular design, following a biomimetic approach that hinges on the observation that G4s are stable secondary structures owing to the ability of Gs to self-associate to form G-quartets, and then of G-quartets to self-stack to form the columnar core of G4s. Therefore, using a synthetic G-quartet as a G4-ligand represents a unique example of biomimetic recognition of G4s, relying on a like-likes-like approach, which is the surest pledge for a very high G4-selectivity.

In this article, we report on the design, synthesis and use of synthetic G-quartet-based ligands, also referred to as TASQs (for template-assembled synthetic G-quartets). These TASQs are the latest prototypes of TASQs, being multivalent TASQs (that is why we refer to them as MultiTASQs) able to be functionalized in situ by click chemistry (both CuAAC and SPAAC) for optical imaging and affinity precipitation purposes. These bioorthogonal investigations thus provides unique information about G4 biology.

Click on the infographic to read the full paper!

G-quadruplexes (or G4s) are four-stranded DNA and RNA structures that fold from guanine (G)-rich sequences. G4 are suspected to play key biological roles in human cells and diseases. Small molecules that selectively target G4s (or G4-ligands) can thus be used as modulators to gain insights into the cell circuitry where G4s are involved. While hundreds of G4-ligands have been designed, synthesized and used, most if not all of them are flat aromatic molecules prone to interact with the duplex-DNA (the major form of DNA within the nucleus), which mechanically decreases their specificity for G4s.

 

About RSC Chemical Biology

Led by Hiroaki Suga (University of Tokyo), RSC Chemical Biology is dedicated to publishing and disseminating the most exceptionally significant, breakthrough findings of interest to the chemical biology community. All submissions are handled by our experienced and internationally recognised Associate Editors. For more information on the journal, please visit the journal homepage.

As a gold open access journal, there are no barriers to accessing content and your research article will reach an international audience. Please note that the article processing charges are waived until mid-2022, so the journal is currently free to publish in.

RSC Chemical Biology is now indexed in the Directory of Open Access Journals (DOAJ), PubMed Central, Scopus and Web of Science: Emerging Sources Citation Index.  Find out more about the journal and submit your work at rsc.li/rsc-chembio

 

RSC Chemical Biology

Royal Society of Chemistry

www.rsc.org

 

 

A fluorescent photoaffinity probe for formyl peptide receptor 1 labelling in living cells

About this article

The paper explores developing a chemical tool to label formyl peptide receptor 1 (FPR1) in cells. FPR1 is a sensor in the human innate immune system, which is our body’s ancient first-line response system to detect pathogens. FPR1 is found in our immune cells; it helps these cells move towards sites of infection by sensing peptides released from bacteria.

However, the role of FPR1 is not so simple. FPR1 has been reported in other cells, such as those lining our mucous membranes (gut, lungs etc.), where it presumably comes into contact with many of our friendly bacteria without causing widespread immune activation. This family of proteins (FPRs1-3) can recognise very different molecules, and how this occurs is only beginning to be explored. FPRs can also cause and suppress inflammation and have been linked to numerous diseases (cancer, autoimmune disease). However, it’s unclear how this occurs and how we might modulate it to treat diseases.

In this paper, we designed a tool to label or tag FPR1 with a dye so we can see this sensor on the surface of cells. Our tool also allows us to detect inhibitors that bind FPR1. A key feature of it, is that it permanently labels FPR1. We expect it will be useful to understand the fundamentals of FPR1 biology and explore how we can treat diseases through molecules that activate or repress this protein.

Image of the article

About RSC Chemical Biology

Led by Hiroaki Suga (University of Tokyo), RSC Chemical Biology is dedicated to publishing and disseminating the most exceptionally significant, breakthrough findings of interest to the chemical biology community. All submissions are handled by our experienced and internationally recognised Associate Editors. For more information on the journal, please visit the journal homepage.

As a gold open access journal, there are no barriers to accessing content and your research article will reach an international audience. Please note that the article processing charges are waived until mid-2022, so the journal is currently free to publish in.

RSC Chemical Biology is now indexed in the Directory of Open Access Journals (DOAJ), PubMed Central, Scopus and Web of Science: Emerging Sources Citation Index.  Find out more about the journal and submit your work at rsc.li/rsc-chembio

 

RSC Chemical Biology

Royal Society of Chemistry

www.rsc.org