In The News

AI / Machine Learning Methods for Enzyme Prediction Featured

The group's work on machine learning methods for enzyme prediction and design in Nature Chemical Biology has been featured in a News & Views in Nature Chemical Biology and by the University.

Antibiotic work Published in Cell Featured

The group's work on new antibiotics has been featured by C+E News and by the University.

Lilly Graduate Prize

Brian Josephson has been given a Lilly Prize for his 1st year graduate work.

Glycogen Control Published in Nature

Matt Bilyard's thesis project in collaboration with Alex Gafitescu, Takuya Machida, Seung Seo Lee and Chris Spicer from the group and the groups of Wyatt Yue (SGC Oxford) and Carme Rovira (Barcelona) has been published online in Nature.

SugaROx - a new spin out

New spin-out from the Davis group, SugaROx, has been highlighted in the MPLS Division Insights newsletter after having been selected for the Royal Society of Chemistry's Investment Catalyst.

Syngenta Postdoctoral Prize

Dr Charlie Fehl was awarded a prize for his talk at the 2017/8 departmental Syngenta Postdoctoral Symposium.

The Making of His isomers in Proteins Highlighted

The demonstration of β,γ-C,N bond formation on protein side chains has been highlighted by a LiveSlides presentation in ACS Central Science.

Living Cotton

Anna Neklesa's work on 'Living Cotton' has been featured in the Nov 30, 2017 edition of Matters.

Simon Nadal + Aziz Khan Lilly

Simon Nadal has been given a Lilly Prize and Aziz Khan a Commendation for their 1st year graduate work.

BGD MAE

BGD has been elected as a member of the Academia Europaea.

Paul Ehrlich Prize 2017

BGD has been awarded the 2017 Prix Paul Ehrlich of the Société de Chimie Thérapeutique (SCT). The prize, for outstanding contributions to medicinal chemistry, is awarded annually at the International Meeting of Therapeutic Chemistry (RICT).

Felix Serratosa Lectures 2017

BGD gave the 2017 22nd Felix Serratosa lectures at the CSIC-Barcelona and ICIQ-Tarragona.

Plant Control via Synthetic Sugar Biology in Nature Highlighted

A strategy for chemical control of plant signaling that increases grain yield and rescues plants from drought published in Nature had been featured on the university's news site and in the The Telegraph Online, The Telegraph, The Daily Mail, and The Financial Times.

Nanobottles for Imaging in Nature Communications Highlighted

A strategy for 'bottling' elements as diverse XRF-phores in celluar biology just published in Nature Commun. has been highlighted in the university's Science Blog.

DPhil Prize for Matt Bilyard

Matt Bilyard was awarded an AstraZeneca D.Phil Symposium Prize for his talk on his graduate work.

Protein Editing Paper in Science

A sidechain C–C-bond-forming method that allows Post-Translational Protein Mutagenesis published in Science has been highlighted in C&E News and in Nature Methods.

Breslow Award 2017

BGD has been awarded the 2017 Breslow Award for Achievement in Biomimetic Chemistry, sponsored by the Ronald Breslow Award Endowment as part of the American Chemical Society 2017 National Awards.

Synthetic Nucleosomes Highlighted

Work from the group on constucting and using synthetic nucleosomes has been Spotlighted in Trends in Biochemical Sciences.

New Vaccine Strategy Highlighted

Work from the group (in collaboration with Glycovaxyn) on a new antibacterial vaccination startegy has been featured in News and Views in Nature Chemistry, the University of Oxford Science Blog, in a Facebook post in Bioconjugate Chemistry and in a Spotlight in ACS Chemical Biology.

Ab Redesign Highlighted by Charity

Work from the group (in collaboration with the Schofield, Mohammed, Benesch and Robinson groups) on redesigning the anti-Her2 antibody Herceptin has been featured by Against Breast Cancer.

Commended Defence

Ben Bower has been given a commendation for his 1st year Graduate Defence / PRS Transfer

Whistler 2016

The International Carbohydrate Organization has awarded BGD the Roy L. Whistler Award in Carbohydrate Chemistry for 2016.

Prize at ICBS 2015

Anuchit Phanumartwiwath has won a prize for his poster and presentation at the 2015 International Chemical Biology Symposium.

Stanford Johnson Lectures 2015

BGD spoke at the 2015 Stanford University Johnson Symposium.

BGD FRS

BGD was elected to the Royal Society in 2015.

Chells featured in the EPSRC Review of the Decade

The group's work on Synthetic Cells (Chells) has been featured in the EPSRC's review of the past decade of science in the January 2015 Issue of Pioneer

Matt Bilyard gets Lilly Prize 2014

Matt Bilyard has been given a Lilly Prize for his 1st year Graduate Defence / PRS Transfer

Practical Wizard

Costi Giurgiu has been given a GSK Prize in Practical Organic Chemistry

CLICK-gong on Telly

The group CLICK-gong was featured on Lewis Episode 1, Series 8.

Bender Lectures 2014

Ben Davis gave the 2014 Bender Distinguished Summer Lectures at Northwestern University.

Lingbing Kong Nature Chemistry Cover Picture

Lingbing Kong's paper on a new antibiotic strategy was the cover of Nature Chemistry.

Lukas Lercher's Angewandte on Suzuki DNA Work Chosen as VIP

Lukas Lercher's paper on Suzuki-biology applied to DNA has been chosen as a Very Important Paper (VIP) by the referees at Angewandte Chemie. It describes the mildest current method for chemically altering DNA.

Lingbing Kong's Nature Chemistry Paper Widely Covered

Lingbing Kong's Nature Chemistry paper has been highlighted in Chemistry World and C&EN and in a News and Views article in Nature Chemistry. It describes a new way to weaken the capsular polysaccharide of Escherichia coli to allow the host's immune system to attack and kill the pathogen. This could pave the way for new antibiotic drugs that make it harder for pathogenic bacteria to develop resistance.

Gold Medal at House of Commons for Chris Spicer

Chris Spicer won the gold medal in the SET for Britain poster competition at the House of Commons by presenting his work on new Pd chemistry for modifying proteins to politicians and a panel of expert judges.

Angewandte on Suzuki PEGylation Highlighted as Hot Paper

Anaelle Dumas, Chris Spicer, Mark Gao and Angel Lin have had their forthcoming paper on Self-Liganded Suzuki protein PEGylation highlighted as a 'hot paper' in Angew. Chem.

Chris Spicer's Arms on the Chem Commun Cover

A paper describing the use of the Suzuki coupling to modify the glycocalyx of E coli by Chris Spicer has featured on the cover of Chem. Commun.

2012 RSC 1st Prize for Chris Spicer

Christopher Spicer won 1st prize at the Royal Society of Chemistry Poster Symposium held in London on Dec 3rd for his work on Pallado-Biology.

Nature Chemistry Tunicamycin paper featured

The recent Nature Chemistry paper on the biosynthesis of tunicamycin has been highlighted in a News and Views article and by the Faculty of 1000.

Pallado Biology is a New Field

A review of the emerging field of artificial biology mediated by Pd chemistry in ChemBioChem has highlighted development of this field by the Davis group. Palladium-mediated carbon-carbon bond formation plays a revolutionary role in advancing organic synthesis and now has the potential to create a new 'Pallado-Biology'.

JACS paper Spotlighted

A recent paper from the BGD group describing a new biocatalytic method for attaching pure glycans to intact antibodies (and has the potential to allow the development of finely-tuned mAb-based drugs) has been spotlighted in JACS.

RSC Bioorganic Prize

Ben Davis has been given the RSC 2012 Bioorganic Award for "his work on carbohydrates and their protein partners revealing fundamental mechanisms behind their structures and bond-forming processes and exploiting this understanding in synthesis and technology.".

Group Work highlighted by UK Research Council

The BBSRC, the UK biological research council, has highlighted work from the group.

Synthetic Histones as Hot Paper in Angew Chem

Justin Chalker and Lukas Lercher's recent work on synthetic histone proteins has been featured as a Hot Paper in Angewandte Chemie. In a collaboration with Nathan Rose from the CJS group, they created synthetic chromosome-associated proteins (histones) that are able to act as proper mimics with so called writer/eraser and reader proteins for the first time.

Chemical Science Cover

Research from the group has been featured on the cover of Chemical Science. The image depicts the key findings in the associated publication in which multiple methods for the conversion of cysteine to dehydroalanine and its use in covalent protein modification are described. The cover artwork was designed by Yuya A. Lin of the Ben Davis group.

Tetrahedron Prize

Ben Davis has been awarded the Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry for 2012.

Justin Chalker Finalist in Reaxys PhD Prize Competition

Justin Chalker was a finalist in the 2012 Reaxys PhD Prize for which he will receive a bursary to travel to the 14th Asian Chemical Congress, on September 7th 2011 in Bangkok.

Poster Prize for Smita Gunnoo

Smita Gunnoo won a poster prize at the 2011 UCB-Celltech UK Science Day.

Nature Chemical Biology Paper Highlighted

Recent work that comes from a collaboration between the Barry group at the US NIH and the Davis group has described the first small molecule that can be used to detect TB. The work, published in Nature Chemical Biology has been featured in Chemistry World, in Nature's Research Highlights, and by the University of Oxford's Science Blog.

Award for Sander van Kasteren

Sander van Kasteren, who worked in the group for his DPhil, has just won a Biochemical Society Early Career Research Award.

Nature Paper Highlighted

Our recent article in Nature was featured in a Nature commentary on the future of Chemistry in the 2011 International Year of Chemistry, on the University website, and in Chemical and Engineering News.

Paper Highlighted in Chemical Communications

Work by Omar Boutureira and co-workers from the BGD group on fluoro-glycoprotein synthesis has been highlighted in Chemical Communications as a HOT Article and also featured on a Cover and ChemComm blog. Researchers developed a tag-and-modify strategy that allows the practical synthesis of homogenous fluorinated glyco-amino acids, peptides and proteins carrying a fluorine label in the sugar, allowing access to the first set of examples of directly radiolabelled ([18F]-glyco)proteins

Paper Highlighted in Nature Glycomics

The recent PNAS article by Katie Doores and co-workers has been highlighted in Nature Glycomics

Paper Highlighted in Nature Chemistry

Our recent article on glycosylated carbon nanotubes was recently featured in Nature Chemistry.

Cover of JACS

A paper that describes the total and reveals the mechanism of pectin self-assembly bulds on the Oxford rich tradition of jam technology and has been featured on the front cover of the June 2 issue of J. Am. Chem. Soc.

BBSRC Innovator of the Year 2010

Ben Davis was selected as a finalist for the BBSRC Innovator of the Year 2010.

Most accessed papers

Two Davis group papers were amongst the most accessed for the year of 2009 in their respective journals: Justin Chalker, Gon̤alo Bernardes and Angel Lin's Cys-modification review in Chem Asian J., and Angel Lin and Justin Chalker's review on Olefin Metathesis in ChemBioChem.

Japan (SSOCJ) Lectureship Award for 2010

Ben Davis has been selected for the Society of Synthetic Organic Chemistry, Japan (SSOCJ) Lectureship Award for 2010 and will give this lecture in September 2010. The last and only other UK recipient was Steve Davies in 1998.

Cover of Carbohydrate Research

Elsevier has selected a group image to be the feature cover for Carbohydrate Research in 2010. The cover illustrates research by the group and was designed by Karl Harrison.

Justin Chalker and Charlotte Wood

Justin Chalker and Charlotte Wood (Part II in 2008/9) have had their paper on Pd-mediated protein reactions highlighted by F1000, by Chemical & Engineering News (Nov 2009), and by ChemCatChem. The research-recently reported in the Journal of the American Chemical Society-features a novel water-soluble catalyst for Suzuki-Miyaura cross coupling. The catalyst enabled the first Suzuki-Miyaura cross-coupling on protein substrates and is also useful in small molecule synthesis.

Award for Filip Wyszynski

Filip Wyszynski won one a 2009 Final Year Graduate Symposia prize awarded by AstraZeneca for his talk on the work that he has been conducting during his DPhil.

Work on HIV Highlighted in the Times

Work by the group on the development of a putative HIV vaccine has been highlighted the Times

Group Research Featured in the Times

In an article entitled 'We see problems, they see solutions' The Times has highlighted some of the group's thoughts on the role and potential of Organic Chemistry in Synthetic Biology.

Ben Davis Gets Quizzed

Ben Davis appeared and was troubled by some worryingly basic questions in the new series of the Channel 5 'What in the World' quiz show screened during the autumn of 2009.

Chemistry World Highlight

Work of the group in Synthetic Biology has been highlighted in an article written in Chemistry World.

Chemical Science Highlight

Work by Justin Chalker, Angel Lin and Omar Boutureira from the group on protein cross metathesis that appears in Chem. Commun. as a hot article has been highlighted by the RSC's popular science news magazine Chemical Science.

Prizes of Keriann Backus and Samantha Shanley

Keriann Backus, a 2nd year student from the group and part of the joint NIH-Oxford programme, was awarded the 'Pfizer Outstanding Poster Prize' at the Bioorganic Gordon Conference held at the Proctor Academy, June 14-19, 2009. Samantha Shanley, a 4th year student from the group was also awarded the Jeremy R. Knowles Memorial Travel Scholarship to attend the same GRC.

Artificial Chemical Cells featured in Nature Chemistry

Work by Paul Gardner (conducted in collaboration with Klaus Winzer from Nottingham) has been highlighted in a News & Views article. Paul's work itself appears in the August issue of Nature Chemistry and reports how they have constructed a lipid-bound protometabolism that synthesizes complex carbohydrates from simple feedstocks, which are capable of engaging the natural quorum sensing mechanism of the marine bacterium Vibrio harveyi and stimulating a proportional bioluminescent response.

Norman Heatley Award for Ben Davis

The Norman Heatley Award has been given to Professor Davis for his outstanding and innovative contributions to protein-carbohydrate chemical biology. The award is new and is given to early career researchers to recognise and promote the importance of inter- and multi-disciplinary research between chemistry and the life sciences.

Ben Davis Profiled in Angewandte Chemie

Prof Gouverneur likes steak & chips, Prof Davis likes bread. Veronique Gouverneur (4 May 2009 issue) and Ben Davis (18 May 2009 issue) have both been selected by Angewandte Chemie for author profiles, which recognise the publication of more than ten papers in the journal since 2000.

Novartis Chemistry Lectureship Award for Ben Davis

The Novartis Institutes for Biomedical Research have selected Ben Davis for a 2009-2010 Novartis Chemistry Lectureship Award. This lecture award, to be given as a series at the Novartis sites around the world, focuses on synthetic organic chemistry and cutting edge chemistry.

PNAS and Chemical & Engineering News Highlight

Work by the Davis group, conducted in collaboration with the Sibson (ROB) and Anthony (Pharmacology) groups, describing new glyconanonparticles that are capable of imaging brain diseases such as MS, has been highlighted by PNAS and Chemical & Engineering News. The paper describing this work appears in the January 6 issue of the Proceedings of the National Academy of Sciences.

Awards for Keri Backus and Mitul Patel

Keri Backus and Mitul Patel were awarded a Commendation for their work on transfer from PRS to DPhil status.

Chemical & Engineering News and Nature Chemical Biology Highlights

A recent publication from the Ben Davis group was highlighted in Chemical & Engineering News and in Nature Chemical Biology. The work was led by Yuya Angel Lin, a Part II student from Keble College. The authors have discovered that allyl sulfides are efficient substrates in aqueous cross-metathesis. The enhanced reactivity derives from a unique sulfur relay of the alkene to the ruthenium catalyst. The high reactivity of allyl sulfides in cross-metathesis was exploited in the first examples of cross-metathesis on a protein surface, setting a new standard in substrate sensitivity and complexity in olefin metathesis and expanding the toolkit for protein modification.

ACS Carbohydrate Division Horace S. Isbell Award for Ben Davis

Ben Davis has been awarded by the ACS Carbohydrate Division the 2008 Horace S. Isbell Award for outstanding contributions to the field of carbohydrate chemistry. The award recognizes carbohydrate scientists under the age of 41 who have demonstrated excellence in the field and show promise of continuing to make high-quality contributions to carbohydrate chemistry and biochemistry. It is the first time someone in the UK has won this honour.

Chemical & Engineering News Highlight

The group's recent publication in J. Am. Chem. Soc., detailing an alternative route to prepare Dehydroalanine (Dha) - an important chemical handle for selectively modifying proteins - has been highlighted in Chemical & Engineering News and in Nature Chemical Biology.

Prize for Samantha Shanley

Samantha Shanley has won the Graduate Presentation prize at the RSC Carbohydrate Group Spring 2008 Meeting held in Oxford on 07-08 April 2008.

Award for Paul Gardner

Paul Gardner, a 3rd year student in the Davis group won first prize for his poster "Quorum Sensing of Formose: Towards Artifical Cell - Natural Cell Communication" at the European Science Foundation meeting on Synthetic Biology.

Nature Protocols Front Cover

A paper by Sander van Kasteren and Holger Kramer, from the Davis group, on the "Synthesis of Glycoproteins" appeared on the front cover of the December issue of Nature Protocols.

Award for Justin Chalker

Justin Chalker has won one of the 2007 Eli Lilly Year Student Awards for Organic Chemistry based on his PRS Transfer Report and Viva.

Synthetic Proteins

Recent work [Nature, 2007, 1105] that may allow the development of synthetic proteins including new types of protein probes has been highlighted.

Angewandte Chemie Communications Frontispiece

A panoramic library: Multiwell library screening of acceptor structures has allowed the identification of the first examples of glycosynthase enzymes that utilize non-natural substrates. In their Communication in Angewandte Chemie, G. Davies, B. Davis, and M. Yang show that the novel specificity, activity, and catalytic efficiency of the mutants are comparable with those of natural glycosyltransferases. The cover shows a 360å¡ view of the multiwell ceiling of Oxford's Radcliffe Science Library.

Angewandte Chemie Communications Frontispiece

Recent work from the groups of Prof. John Simons and Prof. Ben Davis on probing aromatic-sugar complexes has been selected as a frontispiece for Angewandte Chemie. Sugar-arene complexes have been created in molecular-beam experiments and observed by IR ion-dip spectroscopy in the gas phase. These complexes are powerful models of the selective recognition seen in protein-sugar complexes, for example between the galactose-specific lectin from Artocarpus hirsute and MeGal.

Chemical Probes Beat Antibodies At Own Game

The paper in Nature by Sander I. van Kasteren, Holger B. Kramer, Henrik H. Jensen, Sandra J. Campbell, Joanna Kirkpatrick, Neil J. Oldham, Daniel C. Anthony and Benjamin G. Davis which provides a new way of detecting biological structures could help in the fight against disease. The new method, developed by scientists at Oxford University, uses chemistry to assemble proteins into 'protein probes' that can be sent into the body to, for instance, detect inflammation and disease in the brain. > more

Awards for Ben Davis

Ben Davis has been awarded one of the Royal Society of Chemistry's 2005 Corday-Morgan Medals for contributions to synthetic carbohydrate chemistry and glycobiology. He has also been awarded the 2006 International Association for Protein Structure Analysis and Proteomics Young Investigator Award.åÊ

2005 Mullard Award for Ben Davis

Ben Davis is the recipient of the 2005 Royal Society Mullard Award "for hisåÊpioneering work onåÊcarbohydrate and enzyme/proteins and for recognising the commercial potential of his research."

BBSRC Grant

Hagan Bayley, Ben Davis, Neil Oldham and Chris Schofield have been awarded a 5-year grant of å£1.6 million by the BBSRC under the initiative "Selective chemical intervention in biological systems". The funds are for the discovery of small molecules that can be used to explore the roles of the post-translational modification of proteins in living cells. The team aim to create an international resource in this area.

Ben Davis and Ann Dell on BBC Radio 4

Ben Davis and Prof. Anne Dell (Imperial College) discussed the role of carbohydrates on the BBC Radio 4 The Material World programme (2 June 2005).

ACS Chemical Highlights 2004

ACS and Chemical & Engineering News have chosen a paper from Ben Davis' group on Glycodendriproteins as one of the Chemical Highlights of 2004.

Carbs deliver the goods
by Melanie Brazil, Nature Reviews Drug Discovery, November 2004

An approach to drug delivery using novel carbohydrates to carry drugs has recently been described in the Proceedings of the National Academy of Sciences. The method exploits the abundance of lectins, or carbohydrate-binding receptors, on the surface of specific cells. The authors demonstrate the delivery of the cancer drug doxorubin targeted to hepatocytes in a mouse liver tumour model.
Known as the LEAPT strategy, lectin-directed enzyme-activated prodrug therapy is a two-stage delivery system. First, a novel non-mammalian glycosidase enzyme, rhamnosidase, is conjugated to a mammalian sugar; this is taken into the target cell by sugar-mediated receptor-mediated endocytosis, via the asialoglycoprotein receptor, a membrane-bound endocytic lectin found in abundance on the surface of hepatocytes in the liver. The second step involves administering the rhamnose-capped pro-drug; the drug is activated in the target cell once the sugar cap is removed by the pre-delivered rhamnosidase enzyme. The rhamnosidase enzyme was isolated from Penicillium decumbens and its carbohydrate structure was specifically engineered through enzymatic de-glycosylation and chemical re-glycosylation with mammalian sugar residues such as mannose and galactose.
Both in vitro and in vivo techniques proved the delivery of rhamnosidase and prodrug to hepatocytes and demonstrated successful activation of the rhamnose-bound prodrug. The authors tested the therapeutic effectiveness of LEAPT by constructing a doxorubicin prodrug, Rha-DOX, and using it in a hepatocellular carcinoma disease mouse model. After 42 days of therapy, the liver tumour burden was shown to have decreased by almost half compared with the control groups receiving either Rha-DOX or glycosylated rhamnosidase alone.
LEAPT achieves higher concentrations of active drug at the target site through the use of engineered glycosylated enzymes than delivery of drug alone. Assuming that suitable receptors can be identified, delivery to other cell types is possible simply by changing the cognate sugar attached to the enzyme. The use of macrophage-associated carbohydrate receptors to treat macrophage-associated diseases such as lysosomal storage diseases or viral infections could benefit from this approach.

Copycat chemistry disarms bugs
by Emma Davies, Chemistry World, May 2004

Researchers develop protein copies which make bacteria impotent.

Concerns in hospitals about bacterial resistance to current antibiotic treatments continue to rise and global research teams are racing to develop new antibiotics to outwit the pathogens. Now an international team of researchers has approached the problem from a new angle, finding a way to make bacteria impotent by preventing them from binding to cell surfaces.
Many pathogens, including bacteria, bind to host cell surfaces through branched, complex carbohydrate structures on glycoproteins. In a bid to disarm bacteria, the researchers, led by Ben Davis at the University of Oxford, UK, decided to construct copies of these structures. They focused on glycodendrimers, which mimic the branched carbohydrates on glycoproteins. To make copies of glycoproteins, Davis and coworkers then attached glycodendrimers to a protein to form a new class of compounds which they labelled glycodendriproteins.
Bacteria stick to cell surfaces using adhesins, which often form from sugar-binding proteins called lectins. The team claims that its glycodendriproteins attach to lectin adhesins on bacteria and selectively degrade them. ‘This leaves the bug without a method of binding to the host and so leaves it ‘‘handless’’’ explains Davis. ‘Very early observations suggest that the treatment doesn’t seem to kill the pathogens but makes them impotent,’ he says.
According to Davis, ‘a number of pathogens, including viruses, use the same mode of binding: grappling host carbohydrates before infection’. By interfering with the modes of binding, Davis hopes to be able to ‘retool the system to almost any target that uses this strategy, simply by changing the sugars and the level of valency of the glycodendrimer’. He thinks that the glycodendriprotein method may be used to construct mimics of almost any naturally occurring glycoproteins. ‘There is a wealth of potential applications for such structures in chemical glycobiology and related therapeutic areas. We are pretty excited about what these punters could do,’ exclaims Davis. And it seems that other researchers in the field are keen on the work too, with Anne Dell, professor of carbohydrate chemistry at Imperial College London, considering it to offer ‘exciting possibilities’.
Genencor, a US biotechnology company, provided some funding for the work. Davis says that the firm hopes to develop drugs based on the glycodendriproteins. Until now, the project has ‘been driven from the academic side’, he says.

Sticky method to beat germs
by Clive Cookson, Financial Times, 30 April 2004

As bacteria become resistant to existing antibiotics, scientists around the world are searching for new approaches. The latest comes from an international group of chemists from the UK, US and Canada. They propose to use branched sugar-like molecules, called glycodendrimers, to grasp germs in a sticky embrace. Attached to the glycodendrimer is an enzyme that will destroy bacterial proteins.
In laboratory tests the group, led by Ben Davis of Oxford University, showed that the approach worked against a germ called Actinomyces naeslundii. By changing the shape of the glycodendrimer, the chemists hope to make it bind to different bacteria. Their study is published in the Journal of the American Chemical Society.
"We are trying to block infection before it even gets going," says Mr Davis. "The glycodendrimer inhibits the binding but then the enzyme that is attached to the glycodendrimer swings around, chews up the protein on the surface and renders it unable to grab hold of the host it wants to infect." Oxford University: www.ox.ac.uk

Antibacterial sugar-tipped trees
by Philip Ball, Nature, 29 April 2004

Enzymes equipped with grappling hooks can disable pathogenic bacteria, according to Phillip M. Rendle and colleagues. They have found a way to tether a protease (protein-degrading enzyme) to the cell walls of Actinomyces naeslundii bacteria so that the enzyme can break down proteins that the bacteria use to invade their host.
Actinomyces naeslundii stick to human oral cavities and surgical prostheses through adhesin proteins in the bacterial cell walls, which bind to sugar (galactose) molecules. Rendle et al. figured that galactose groups attached to proteases would enable the enzymes to latch on to A. naeslundii , which would not only suppress the bacterium's stickiness by plugging their adhesin sites but would also wreak havoc when the enzyme got to work on the bacterial cell-wall proteins.
A single galactose tether is not enough, however. So Rendle et al. fixed branched tethers (dendrons) at selected positions on the proteases. Dendrons with two, three or four sugar tips give the enzyme a secure hold, with two tips being optimal for this bacterium. In preliminary tests, these modified proteases appear to inhibit A. naeslundii at concentrations of just 20 nanomolar.

New approach to antobiotics: synthetic carbohydrate-protein conjugate inhibits bacterial infection
by Celia M. Henry, Chemical & Engineering News, 12 April 2004

A novel type of conjugate of carbohydrates and protein--known as a "glycodendriprotein"--may provide a new route to antibiotics.
Chemist Benjamin G. Davis of the University of Oxford, in England; microbiologist Marjorie M. (Kelly) Cowan of Miami University of Ohio, Oxford; and coworkers have shown that by linking branched carbohydrate-tipped structures known as glycodendrimers to a protein-degrading enzyme, they can inhibit the infectivity of the bacterium Actinomyces naeslundii [J. Am. Chem. Soc., 126, 4750 (2004) ].
Davis and his colleagues are targeting bacteria earlier in the infection process than most antibiotics do. "We're trying to block infection before it even gets going," he says. "The glycodendrimer inhibits the binding, but then the enzyme that is attached to the glycodendrimer swings around, chews up the protein on the surface, and renders it unable to grab hold of the host it wants to infect."
The glycodendrimers consist of sugar molecules on the tips of an antenna-like scaffold formed by such dendrimeric core molecules as TREN [tris(2-aminoethyl)amine] or mesitylene. Testing glycodendrimers with different numbers of antennae, the researchers found that a pair of antennae, with a total of two sugar residues, was the optimal number for the antibacterial system. For an alternative carbohydrate-binding protein, they found that a pair of branched antennae displaying four sugars was best.
The glycodendrimers are attached to the protease subtilisin through a cysteine linkage. Because subtilisin contains no naturally occurring cysteines, the positions where cysteines are inserted determine the locations of the carbohydrate on the protein. The carbohydrate targets and binds to receptors on the surface of A. naeslundii . Then the subtilisin chews up the protein adhesin on the bacterial cell surface. The carbohydrates successfully direct an otherwise nonspecific protease to the target protein. "We deliberately chose an enzyme that was very broad so that all we had to do was retool the enzyme with the appropriate targeting ligand," Davis says.
Davis believes the approach of synthesizing glycoproteins is flexible enough to be applied to a variety of systems. "There are a vast array of carbohydrate-binding proteins out there," he says. "You can basically pick the carbohydrate you need and then retool the end of the dendrimer for that function."
Carolyn R. Bertozzi, professor of chemistry at the University of California, Berkeley, who also studies glycoconjugates, calls this work an interesting approach to blocking bacterial adhesion and targeting receptors for degradation. "While bacterial proteins can become resistant to drugs via rapid mutation, the actual carbohydrate-binding residues in these bacterial adhesins are under pressure to remain conserved, as they are vital for the colonizing activity of the bacterial cell," Bertozzi says. "Thus, any approach that targets the carbohydrate-binding activity is less likely to suffer from the selection of resistant strains. Although its reduction to clinical practice is a ways off, as a concept, I think this is an interesting combination of antiadhesive therapy and receptor-mediated drug delivery that will prompt new ways of thinking about antibiotic design."

Last updated: 08-12-20

Prof Benjamin G. Davis
University of Oxford
Chemistry Research Laboratory
Mansfield Road
Oxford, OX1 3TA, UK
Phone: + 44 (0)1865 275652
Fax: + 44 (0)1865 275674
Ben.Davis@chem.ox.ac.uk