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Editor’s Collection: Elizabeth Krenske

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 Elizabeth Krenske 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.

Elizabeth’s Selection:

Photochemical [2+2] Cycloaddition Reaction of Carbonyl Compounds with Danishefsky Diene

Dian Agung Pangaribowo and Manabu Abe

Elizabeth’s comments: “This work by Abe and Pangaribowo reveals that photochemistry can be harnessed to propel Danishefsky’s diene towards a new functionalisation manifold. It also reports the first stereocontrolled synthesis of the until-now elusive cis isomer of Danishefsky’s diene.”

Find out more in our interview with the authors

 

Decomplexation as a rate limitation in the thiol-Michael addition of N- acrylamides

Joseph S. Brown, Andrew W. Ruttinger, Akash J. Vaidya, Christopher A. Alabi and Paulette Clancy

Elizabeth’s comments: “In this thought-provoking contribution, Clancy and coworkers show that in Michael additions involving certain fluorous hydroxylated thiols, the rate-limiting step is not the addition itself, but the liberation of the product from the complex that it forms with other co-reactants. This work adds an intriguing new dimension to the mechanistic understanding of this important class of reactions.” 

Find out more in our interview with the authors

 

Chemical methods for modification of proteins   

Neelesh C. Reddy, Mohan Kumar, Rajib Molla and Vishal Rai

Elizabeth’s comments: “In this review, Rai and coworkers survey key milestones in the field of protein chemical modification. With a special focus on the role of protein architecture in modulating innate reactivity, this work highlights the challenges and opportunities that chemists face when pursuing selective protein modification.”

Find out more in our interview with the authors

 

Tuning activation and self-immolative properties of the bioorthogonal alkene–azide click-and-release strategy

Jessica M. Fairhall, Madoka Murayasu, Sumit Dadhwal, Sarah Hook and Allan B. Gamble

Elizabeth’s comments: “Here, Gamble and coworkers push the boundaries of azide/alkyne cycloaddition kinetics with their development of a new series of click-and-release reactions. The work is a neat application of physical organic chemistry to expand the bioorthogonal chemist’s toolbox.”

Find out more in our interview with the authors

 

Meet the Editor:

Elizabeth Krenske is an Associate Editor for Organic & Biomolecular Chemistry since 2019. Elizabeth is an Associate Professor at the University of Queensland, Australia, where her research focuses on the computational study of organic reactions and modelling of drug molecules and interactions.

After starting out her career in chemistry as an undergraduate at the University of Queensland, Elizabeth undertook a PhD in the field of synthetic main-group chemistry at The Australian National University’s Research School of Chemistry, under the supervision of Professor S. Bruce Wild. She spent a further two years carrying out postdoctoral research at the Australian National University, before receiving a Fulbright Scholarship and commencing postdoctoral studies at UCLA with Ken Houk. Elizabeth returned to Australia in 2009 as an Australian Research Council (ARC) Australian Postdoctoral Fellow at the University of Melbourne, and moved to The University of Queensland in 2012 as an ARC Future Fellow. She is currently an Associate Professor and Strategic Research Fellow in the University of Queensland School of Chemistry and Molecular Biosciences. To find out more about Elizabeth and her research,  please visit her webpage.

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Editor’s Collection: Meet the authors – Brown, Ruttinger, Vaidya, Alabi and Clancy

From left to right: Brown, Ruttinger, Vaidya, Alabi and Clancy

Introducing the researchers: 

Joseph S Brown is currently a Postdoctoral Associate at the Massachusetts Institute of Technology in Professor Bradley Pentelute’s Lab in Chemistry. He received his B.Sc. in Chemical and Biomolecular Engineering from North Carolina State University in 2013 with Valedictorian Honors. At Cornell University, he earned his Ph.D. in Chemical and Biomolecular Engineering working with Professor Christopher Alabi on the structural and biophysical characterization of sequence-defined oligothioetheramides as a National Science Foundation (NSF) Graduate Research Fellow. He plans to apply his skills in synthetic chemistry, biophysical characterization, and biochemistry to aid the drug discovery of biologics focusing on the therapeutic disruption and modulation of protein-protein interactions.

Andrew W Ruttinger is currently a Ph.D. candidate in Chemical and Biomolecular Engineering at Cornell University, with Professor Paulette Clancy on the development of low-carbon and renewable energy technology. He earned his Bachelor of Engineering in Chemical Engineering from the University of Western Ontario, Canada. Upon graduation, Andrew plans to work in science policy, using his experience in developing green technology towards protecting Canada’s environment and climate.

Akash Vaidya received his B.S. in Chemical Engineering from Cornell University, where he was an undergraduate researcher for Professor Christopher Alabi. He spent two summers as a undergraduate research fellow with the Lyssiotis Research Group at the University of Michigan Medical School. Akash is currently pursuing his Ph.D. in Chemical and Biomolecular Engineering at the University of Delaware, where he plans to design (bio)polymeric materials for medical applications and lead outreach programs to promote diversity and inclusion in engineering.

Christopher Alabi is the Nancy and Peter Meinig Family Investigator in the Life Sciences at the Robert Frederick Smith School of Chemical and Biomolecular Engineering at Cornell University. Research in the Alabi lab seeks to utilize synthetic and analytical tools to understand how the composition and sequence of a macromolecular chain affects its chemical, structural and biological properties with an eye towards engineering sustainable materials and biomolecular therapeutics.

Paulette Clancy is a Professor and inaugural Head of the Department of Chemical and Biomolecular Engineering at the Johns Hopkins University. She is also the Samuel and Diane Bodman Professor Emerita of Chemical Engineering at Cornell. Her group develops new algorithms to advance our ability to make accurate models of materials, especially electronic materials and sustainable energy systems.  More recently, her group is developing new machine learning techniques to accelerate the search for optimal materials processing protocols and new materials.

 

What inspired your research in this area?

We were inspired to pursue this work because it promised to unlock new and exciting chemical reaction schemes including automated, robotic, and/or combinatorial syntheses using the thiol-Michael addition. While we chose to study oligothioetheramides (oligoTEAs) in this work, we expect that the new mechanistic understanding of the thiol-Michael addition reaction that we have uncovered will be broadly applicable, allowing us to create designer monomers for other types of materials and polymer science applications.

 

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

While surprising at first, our most interesting finding was that physical associations could be strong enough to dictate rate-limiting steps within the reaction mechanism. Other groups have observed this for acrylates (Desmet et al., Polymer Chemistry (2017)), but the addition of this work has clarified our understanding of the exact mechanism, including product decomplexation. It was also exciting to see the nearly quantitative agreement between experiments and accurate DFT calculations coupled to a method of finding energy barriers (Nudged Elastic Band) that give exquisitely detailed insight into the mechanism that underlies this popular Michael addition reaction.

 

What are you going to be working on next?

We believe that sequence-defined materials like oligoTEAs could offer a promising new approach to controlling the design of new biomaterials. Precision biomaterials are still finding their niche, but are well-positioned to contribute as therapeutics, diagnostics, catalysts, and others. Many of these applications rely on selective and high-affinity molecular recognition events, which is our focus at this time. Computationally, we are working on a new approach that deploys machine learning to accelerate discovery of sequence-controlled oligoTEAs to match a given objective. Even with just 12-15 “beads” on the oligoTEA backbone, the size of the combinatorial problem precludes a trial-and-error search, whether computationally or experimentally.  Machine learning can help us tame this otherwise overwhelming design space.

 

Read the full article: Decomplexation as a rate limitation in the thiol-Michael addition of N- acrylamides

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Editor’s Collection: Meet the authors – Abe and Pangaribowo

From left to right: Dian Agung Pangaribowo and Manabu Abe

 

Introducing the researchers:

Manabu Abe was born in Sakai City, Osaka Prefecture, Japan. He received his Ph.D. from the Kyoto Institute of Technology (KIT), Professor Akira Oku, in 1995, studying the oxidative ring-opening reaction of cyclopropanone acetals and its application to organic synthesis. After 12 years in Osaka University as an assistant professor and associate professor, he moved to Hiroshima and became a full professor in Organic Chemistry at the Department of Chemistry, Graduate School of Science, Hiroshima University (HIRODAI) in 2007. His research focuses on reactive intermediates chemistry, especially on diradicals, organic photochemistry and unusual molecules.

Dian Agung Pangaribowo received his Master’s degree in 2013 from Airlangga University, Surabaya, Indonesia. He is currently a doctoral program student at the department of chemistry, graduate school of science, Hiroshima University, under the supervision of professor Manabu Abe. His current research focuses on photochemical [2+2] cycloaddition reaction of Danishefsky-Kitahara diene with a carbonyl compound.

 

What inspired your research in this area?

Electronically excited-state molecules, which are generated by photolysis and have different electronic characteristics from their ground-state molecules, possess strong potentials to produce unexpected reactions and products that are not expected in the thermolysis of the same combination of compounds. In this study, as a case study, we are very much interested in exploring regio-, stereo-, and chemo-selectivities in the photolysis of Danishefsky-Kitahara diene with carbonyl compounds, whose selectivities should be different from those in the thermolysis.

 

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

Two important findings emerged in the photolysis of the trans-configured Danishefsky-Kitahara diene with benzophenone; (1) a clean isomerization from the trans-form to the cis-form of the diene, which has not been achieved so far in thermal reactions. (2) Potentially bioactive compounds, oxetanes, are formed in high yields. The chemo-selectivity of the photochemical reaction is totally different from the Lewis acid-promoted thermal reaction.

 

What are you going to be working on next?

Since the Danishefsky-Kitahara diene is synthetically useful compound and considered as an “electron-rich” compound, we are interested in investigating the possibility of the photoinduced electron transfer reactions of the diene to find new types of synthetically useful chemical reactions.

 

Read the full article: Photochemical [2+2] Cycloaddition Reaction of Carbonyl Compounds with Danishefsky Diene

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Editor’s Collection: Meet the authors – Fairhall, Murayasu, Dadhwa, Hook and Gamble

From left to right: Fairhall, Murayasu, Dadhwal, Hook and Gamble

Introducing the researchers: 

Dr Jessica Fairhall received her PhD in 2020 from the University of Otago, under the supervision of Dr Allan Gamble and Prof. Sarah Hook. Her PhD focused on the bioorthogonal reaction between aryl azides and trans-cyclooctenes as a technique for cancer-specific prodrug activation. During her PhD she also received a 4 month fellowship to conduct research at Novartis Institutes for BioMedical Research in Emeryville California. She is currently working as a Clinical Editor for the New Zealand Medicines Formulary, and is starting a new role at the University of Otago as a Research Fellow in October.

Madoka Murayasu graduated with a BPharm (Hons) First Class in 2016 from the University of Otago. Her Honours project focused on bioorthogonal prodrug activation strategies. Madoka is currently working as a community pharmacist in New Zealand.

Dr Sumit Dadhwal completed his PhD at the University of Otago in 2018 with Dr. Allan Gamble and Prof Sarah Hook. His PhD research focused on the development of stimuli-responsive biomaterials for drug delivery applications. Currently he is working as a Research Fellow at the University of Otago.

Professor Sarah Hook is Chair of Biopharmaceutics at the School of Pharmacy, University of Otago in Dunedin, New Zealand. She received her PhD in 1996 from the Department of Microbiology and Immunology at the University of Otago. She joined the faculty of the School of Pharmacy in 2001. Research interests include the development of one-shot sustained release, particulate and responsive formulations for the delivery of small and large molecule therapeutics. Her research in the field is aided by her knowledge and experience in the fields of immunology and pharmaceutical formulation science. She has published more than 100 papers since joining the School of Pharmacy.

Dr Allan Gamble received his PhD in organic chemistry in 2008 from the University of Wollongong in Australia with Prof Paul Keller. He then moved to Canberra to take up a postdoctoral position at the Australian National University with Prof Chris Easton. Here he worked on peptide hormone regulation until late 2010. In 2011, he was awarded a Sir Keith Murdoch Postdoctoral Fellowship through the American Australian Association to work with Prof Paul Wender at Stanford University on developing new drug delivery strategies. In May 2012 he took up the position of Lecturer in the School of Pharmacy at the University of Otago and was promoted to Senior Lecturer in 2016. His research interests are in the areas of bioorganic and physical organic chemistry and drug delivery.

 

What inspired your research in this area?

Our research group has a strong focus in bioorganic and physical organic chemistry, and applying our skills to the development of new drug delivery strategies (prodrugs, hydrogels, nanoparticles). Over the past 8 years we have been influenced and motivated by the chemistry of Professors Carolyn Bertozzi, Joseph Fox and Marc Robillard. The initial inspiration stems from Dr Gamble’s research experience as a postdoc in the Wender group. Here he developed a passion for drug delivery and bioorthogonal chemistry. While preparing applications for an independent career in academia, Dr Gamble formulated an idea that would use the strain-promoted alkene-azide cycloaddition coupled with self-immolative linker chemistry to deliver cytotoxic drugs for cancer therapy. The alkene-azide cycloaddition appeared to have been left-out of the bioorthogonal reaction toolkit due to the formation of unstable adducts (e.g., 1,2,3-triazoline and imine), therefore providing an opportunity to establish a research group with a primary focus of developing this chemistry.

 

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

Our initial work in this area (Chem. Sci. 2015, 6, 1212-1218; Bioconjugate Chem. 2018, 29, 324-334) provided proof-of-principle for the click-to-release activation of a prodrug in vitro using the alkene-azide cycloaddition. However, the physical organic chemistry components of the reaction, namely the kinetics for the click and release steps were not ideal for bioorthogonal applications in vivo. In the current study (Org. Biomol. Chem., 2020, 18, 4754-4762), we have been able to establish the fastest-to-date strain-promoted alkene-azide cycloaddition that also maintains a rapid drug release profile. The rate constants for the click and subsequent release steps pave the way for in vivo studies that will benefit from using this chemistry.

 

What are you going to be working on next?

We continue to work towards improving the physical organic chemistry components of the alkene-azide cycloaddition so that we can further extend its click-to-release bioorthogonal chemistry applications. Using the results of this recent study we are investigating in vivo prodrug activation in mice, and applying the alkene-azide click-to-release strategy to drug delivery systems (e.g. hydrogels and nanoparticles).

 

Read the full article: Tuning activation and self-immolative properties of the bioorthogonal alkene–azide click-and-release strategy

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Editor’s Collection: Meet the authors – Reddy, Kumar, Molla and Rai

From left to right: Reddy, Molla, Kumar and Rai

Introducing the researchers: 

Neelesh C. Reddy obtained his B.Sc. from Deogiri College and M. Sc. from Dr. Babasaheb Ambedkar Marathwada University Aurangabad, Maharashtra, India. For his Ph.D., he joined the research group of Dr. Vishal Rai at the Indian Institute of Science Education and Research Bhopal, India. Neelesh is developing modular chemical technologies for precision engineering of native proteins. Further, he is using the platform for the synthesis of homogeneous antibody-drug conjugates for directed cancer chemotherapeutics.

Rajib Molla obtained his B. Sc. (2016) from West Bengal State University and M. Sc. (2018) from West Bengal State University. At present, he is pursuing his Ph.D. under the supervision of Dr. Vishal Rai at the Indian Institute of Science Education and Research Bhopal. He is applying his experience in organic and organometallic chemistry to develop new chemical methodologies for protein bioconjugation.

Mohan Kumar obtained his B.Sc. (2016) from Lucknow University and M.Sc. (2018) from the National Institute of Technology Manipur, India. In 2019, he joined the research group of Dr. Vishal Rai at the Indian Institute of Science Education and Research Bhopal, India. In his Ph.D., he is developing chemical technologies for the modification of proteins in live cells.

Vishal Rai received his Ph.D. in 2008, working in the area of asymmetric synthesis from the Department of Chemistry, Indian Institute of Technology Bombay (India), under the supervision of Prof. I. N. N. Namboothiri. In 2008, he joined the group of Prof. Andrei Yudin in the Department of Chemistry, University of Toronto (Canada), to work on chemoselective methodologies and peptide macrocycles. Vishal started his independent career in the Department of Chemistry, Indian Institute of Science Education and Research Bhopal (India) as Assistant Professor in 2011 and became Associate Professor in 2017. He is the recipient of Swarnajayanti fellowship, Ramanujan fellowship, and DAE Young Scientist Award. In 2018, he established Plabeltech Private Limited, a company strengthened by the protein labelling technologies developed by his team. His research group is developing chemical technologies for precision engineering of native proteins. Further, they are translating these platforms to enable directed and precision therapeutics.

 

What inspired your research interests in chemical protein modification?

The knowledge to enable selective modification of native proteins could provide a tremendous boost to the biotechnology and healthcare sectors.

 

What primary research are you carrying out in the area?

Our group is developing chemical technologies for precision engineering of proteins. We are excited about its potential to empower directed therapeutics and believe that it can enable precision therapeutics with small molecules one day.

 

How do you hope this review will help and inspire future research in the area?

This review intends to provide a chemist’s perspective of “what, why, and how” in the field of protein bioconjugation.

 

Read the full article: Chemical methods for modification of proteins

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Editor’s Collection: Meet the authors – Appel et al.

The Appel Research Group

From left to right: Eric A. Appel, Anton A. A. Smith, Caitlin L. Maikawa and Gillie A. Roth

 

Introducing the researchers:
Eric A. Appel is an Assistant Professor of Materials Science & Engineering at Stanford University. He received a BS in Chemistry (2008) and MS in Polymer Science (2008) from Cal Poly San Luis Obispo, and a PhD in Chemistry (2013) from Cambridge University. His research group at Stanford integrates concepts and approaches from supramolecular chemistry and polymer science to develop (bio)materials that can be used as tools to better understand fundamental biological processes and to engineer advanced healthcare solutions.

Anton A. A. Smith holds a PhD from Aarhus University, Denmark. He will soon be joining the Technical University of Denmark (DTU) where he will be continuing research at the interface of chemistry and biology.

Caitlin L. Maikawa received her BASc (2016) in Chemical Engineering from the University of Toronto. She is currently working on her PhD in Bioengineering at Stanford University with Prof. Eric Appel. Her PhD research focuses on using supramolecular biomaterials to create improved insulin formulations for the treatment of diabetes.

Gillie A. Roth received her B.S. (2015) in Bioengineering from UC San Diego and then completed her PhD in Bioengineering at Stanford University with Eric Appel. Her PhD research focused on designing biomaterials to modulate the pharmacokinetics of therapeutics across diverse disease indications.

 

What inspired your research in this area?
We were already using a conjugate of cucurbit[7]uril with poly(ethylene glycol) (CB[7]-PEG) as a “designer” excipient in insulin formulations (https://www.nature.com/articles/s41551-020-0555-4, https://www.pnas.org/content/113/50/14189.short) to improve insulin stability and alter pharmacokinetics. In this work we figured we could exploit the affinity of CB[7] for the N-terminal phenylalanine on insulin as a tool for insulin modification. Covalent PEG conjugates of insulin had already been examined on numerous occasions in the literature, with insulin bioactivity being heavily dependent on the site of conjugation (steric repulsion from modification in the wrong spot can completely remove activity). Conjugation to the A chain N-terminal glycine significantly reduced activity, making it an interested target for stimulus responsive activation of insulin. Unfortunately, the existing means of selectively functionalizing this site are cumbersome because the preferred site of modification on insulin is the B chain N-terminal phenylalanine. The strong, selective non-covalent binding of CB[7] to this N-terminal phenylalanine presented itself as a practical shortcut to block the nucleophilicity of this site, thereby acting as a non-covalent protecting group, to allow for selective modification of the A-chain N-terminal glycine by simple acylations.

 

What do you personally feel is the most interesting outcome of your study?
For insulin specifically, this work enables a simple approach to selectively functionalize the A chain, which has traditionally been very challenging to modify on account of its poor nucleophilicity compared to the B chain. Our approach shortens the synthetic route towards selective conjugation at this site as the self-assembly provides direct blocking of the site in the reaction flask with simple mixing, but the dynamic non-covalent binding allows for removal of the CB[7] protection directly during purification without need for a deprotection step.

For a broader perspective, non-covalent protection groups in protein and peptide conjugation chemistry are virtually unexplored, and we show that CB-based host-guest complexation provides a simple and effective approach to blocking of aromatic amino acids to drive selective modification elsewhere on the peptide/protein. This approach is potentially applicable to selective conjugation with an array of proteins or peptides.

 

What directions are you planning to take with your research in future?
Insulin conjugates, and possibly stimulus responsive activation, along with excipients in formulation are areas we are very excited about. We imagine there is ample room for developing both the chemistry and clinically relevant translational research using this new approaches to non-covalent protection.

 

Read the full article: Site-selective modification of proteins using cucurbit[7]uril as supramolecular protection for N-terminal aromatic amino acids

 

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Editor’s Collection: Meet the authors – Sperry and Devlin

Rory Devlin (Left) and Jonathan Sperry (Right)

Introducing the researchers:

Rory Devlin received a BSc (Hons) from The University of Auckland in 2017. Currently, he is pursuing his PhD at the same institution under the supervision of Assoc. Prof. Jonathan Sperry, exploring novel biomimetic rearrangements towards the synthesis of alkaloid natural products.

 

Jonathan Sperry completed his Ph.D at the University of Exeter, working on the biomimetic synthesis with Professor Chris Moody. After postdoctoral research with Dame Margaret Brimble FRS at the University of Auckland, he was appointed to a lectureship at the same institution in 2009. Jon was a Royal Society of New Zealand Rutherford Discovery Fellow from 2014-2019.

 

What inspired you to write this review?

Our interest in the nudicaulins was mainly from a synthetic perspective and in particular, validating the unique cascade process in their proposed biosynthesis. We were surprised nobody had written about the nudicaulins before, especially given their fascinating history.

 

What experimental research are you carrying out in the area?

We are using the nudicaulin structure as a lead for drug discovery – the synthetic route to the natural product is very amenable to analogue design. We are also collaborating with Professor Bernd Schneider at the Max Planck Institute for Chemical Ecology to better understand the role and distribution of the nudicaulins.

 

How do you hope this review will inspire future study?

Synthetic chemists’ interest in natural products is generally focused on structure and bioactivity, but this is just the tip of the iceberg – there is so much more to learn and the nudicaulins are a great example. When we choose a natural product for synthesis studies, we now aim to understand why the organism produces the compound which has has led to some great collaborations and research projects I would have never had imagined being involved in a few years ago.

 

Read the full article: The curious yellow colouring matter of the Iceland poppy

 

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Editor’s Collection: Meet the authors – Fascione et al.

From left to right: Robin Brabham, Tessa Keenan and Martin Fascione

Introducing the researchers:

Martin Fascione received his Ph.D. from the University of Leeds in 2009, working with W. Bruce Turnbull on synthetic carbohydrate chemistry. Following a Marie Curie fellowship with Prof. Steve Withers, FRS, in Vancouver and Prof. Gideon Davies, FRS, at the University of York (2012-2014), he took up a lectureship within Chemistry at York in August 2014. His research interests include the chemical glycobiology of rare sugars, synthetic carbohydrate chemistry, and the chemical/enzymatic modification of proteins.

 

Robin Brabham completed his PhD studies in the Fascione group in 2020. His thesis explored the use of amber stop codon suppression as part of new methods for the incorporation of reactive aldehydes into proteins for bioconjugations.

 

Tessa Keenan received her PhD in 2017 from the University of York on protein O-mannosylation. Since completing her PhD, she has undertaken postdoctoral training in the Fascione group in the areas of chemical glycobiology and protein bioconjugation.

 

What inspired your research in this area?

We recently developed an exciting method for modifying proteins (Chem. Sci., 2018, 9, 5585-5593), using reactive a-oxo aldehydes in proteins, but a challenge of this work was extending it to any position within the protein. Periodate oxidation of vicinal diols, or amino alcohols has long been a common method to generate aldehydes in sugar and protein chemistry, it therefore seemed an obvious next step to incorporate such a motif into an unnatural amino acid.

 

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

The ability to incorporate the a-oxo aldehyde internally within proteins is potentially very powerful for future bioconjugation studies. However, the most interesting outcome of the paper is arguably the realisation that the classical unmasking of aldehydes by sodium periodate oxidation is hindered in PBS, a very common buffer for handling proteins.

 

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

Our primary focus is the study sugars at the interface between chemistry and biology, with an emphasis on understanding the roles they play in disease and using this knowledge to develop innovative new therapeutics. To achieve this goal we have been developing new methods for synthesising sugars and modifying proteins using aldehyde handles, and are currently using this toolkit to address unanswered questions in a wide range of diseases, including prostate cancer and leishmaniasis.

 

Read the full article: Rapid sodium periodate cleavage of an unnatural amino acid enables unmasking of a highly reactive α-oxo aldehyde for protein bioconjugation

 

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Editor’s Collection: Meet the authors – Saito and Yagai

Takuho Saito and Shiki Yagai

Introducing the researchers:

Takuho Saito was born in 1996 in Tochigi, Japan. He graduated Chiba University in 2019, and is currently a master’s student under the guidance of Prof. Shiki Yagai at the same University.

Shiki Yagai was born in 1975 in Japan and received his PhD in 2002 at Ritsumeikan University. Then he directly became an assistant professor at Chiba University, and became an associate professor in 2010. In July 2017, he became a full professor in Chiba University. Find out more on his lab webpage.

 

What inspired your research in this area?

We are always inspired by natural molecules and macromolecules to organize into intricate nanostructures, wherein non-covalent interaction such as hydrogen bonds play important role to achieve hierarchical assembly of structures.

 

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

The answer is definitely the fact that just changing the direction of amide groups remarkably improved the thermal stability of our nano-aggregates, as prof. Hackenberger said.

 

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

We are very much interested in the introduction of more amide groups to further improve thermal stability. At the same time, we are interested in the interplay of photoisomerization of azobenzene units and supramolecular chirality.

 

Read the full article: Hierarchical self-assembly of an azobenzene dyad with inverted amide connection into toroidal and tubular nanostructures

 

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Editor’s Collection: Meet the authors – Nielsen, Gothelf and Clo

From left to right: Kurt Gothelf , Emiliano Clo and Thorbjørn Nielsen

 

Introducing the researchers:

Thorbjørn Nielsen: Obtained an MSc. Degree from the Gothelf lab in 2016. He then enrolled in a joint PhD program between Novo Nordisk in Måløv and Aarhus University where he spent half of his time in each place. He graduated in 2020 and is currently a postdoc at the Gothelf lab.

Kurt Gothelf graduated in 1995 from the group of Professor K. A. Jørgensen at Aarhus University. Following a post doctoral stay in Professor M. C. Pirrung’s group at Duke University, USA, he joined the faculty at Aarhus University in 2002 as an Associate Professor. Since 2007 he has been a Full Professor working with bioconjugation, DNA nanotechnology and biosenors. Find out more on his lab webpage.

Emiliano Clo obtained his PhD in Organic Chemistry in 2006 from the Gothelf lab at Aarhus University. He took post doctoral positions from 2007-9 with Prof. Knud Jensen at University of Copenhagen and from 2009-12 in Prof. Henrik Clausen’s Copenhagen Center for Glycomics, spending the last year of which as Research Associate Professor. From 2012, Emiliano works as a Senior Research Scientist at Novo Nordisk’s Research Chemistry Unit.

 

What inspired your research in this area?

Bioconjugation is challenging and both at Novo Nordisk and in the Gothelf group at Aarhus University we follow closely the development of bioconjugation techniques. Itaru Hamachi’s work on directed conjugation strategies has definitely been a steady influence over the years. But, the present study is really an amalgamation of ideas from many sources.

 

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

The most surprising observation was to learn that the conjugation pattern was identical, in spite of the varying the length of the three reagents studied.

 

How do you feel your research has benefitted from collaborating between industry and academia? 

It has been of key importance to the project. Thorbjørn Nielsen (who got his MSc. with Prof. Gothelf) brought the required skillset to Novo Nordisk. Novo Nordisk then provided the materials and equipment required for this project. Together we could pull all the support the projected needed: MS-MS and SPR expertise at Novo Nordisk; cell assays and FACS from Aarhus Unversity. Last, but not the least, Apigenex, Novo’s long-time CRO partners, synthesized the reagents needed.

 

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

Concerning bioconjugation, our future aims are twofold. First, to find reactions that can label proteins quantitatively; second, to devise reagents and protocols that can be applied to more complex proteins or in more complex matrices.

 

Read the full article: disulphide-mediated site-directed modification of proteins

 

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

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