Peter Both

Axxence · R&D

Altered glycoprotein expression is an undisputed corollary of cancer development. Understanding these alterations is paramount but hampered by limitations underlying cellular model systems. For instance, the intricate interactions between tumour and host cannot be adequately recapitulated in monoculture of tumour-derived cell lines. More complex co...

Interactions between cells fundamentally impact biological processes. In cancer development, such interactions define key stages of disease that cannot be adequately recapitulated in cell monoculture. Complex co-culture studies have been key to unraveling the complexity of these processes, usually by sorting cells and transcriptome or bulk proteome...

Promiscuous activity of a glycosyltransferase was exploited to polymerise glucose from UDP-glucose via the generation of β-1,4-glycosidic linkages. The biocatalyst was incorporated into biocatalytic cascades and chemo-enzymatic strategies to synthesise...

Pseudaminic acid (Pse5Ac7Ac) is a non-mammalian sugar present on the cell surface of a number of bacteria including Pseudomonas aeruginosa, Campylobacter jejuni and Acinetobacter baumannii. However, the role Pse5Ac7Ac plays in host-pathogen interactions remains underexplored, particularly compared to its ubiquitous sialic acid analogue Neu5Ac. This...

Fluorinated sugar-1-phosphates are of emerging importance as intermediates in the chemical and biocatalytic synthesis of modified oligosaccharides, as well as probes for chemical biology. Here we present a systematic study of the activity of a wide range of anomeric sugar kinases (galacto- and N-acetylhexosamine kinases) against a panel of fluorina...

S. pneumoniae is a major human pathogen with increasing antibiotic resistance. Pneumococcal vaccines consist of capsular polysaccharide (CPS) or their related fragments conjugated to a carrier protein. The repeating unit of S. pneumoniae type 14 CPS shares a core structure with the CPS of Group B Streptococcus (GBS) type III: the only difference is...

The human cell surface trisaccharide motifs globotriose and P1 antigen play key roles in infections by pathogenic bacteria, which makes them important synthetic targets as antibacterial agents. Enzymatic strategies to install the terminal α1,4-galactosidic linkage are very attractive but have only been demonstrated for a limited set of analogues. H...

The β-1,4-glucose linkage of cellulose is the most abundant polymeric linkage on earth and as such is of considerable interest in biology and biotechnology. It remains challenging to synthesize this linkage in vitro due to a lack of suitable biocatalysts; the natural cellulose biosynthetic machinery is a membrane-associated complex with processive...

Sialic acids are cell surface sugars present in many animal glycoproteins and are of particular interest in biopharmaceuticals, where lack of sialylation can reduce bioactivity. Here we describe how α-2,6-sialyltransferase from Photobacterium damselae can be used to markedly increase sialylation of CHO produced alpha-1-antitrypsin. Detailed analysi...

N-Glycolylneuraminic acid (Neu5Gc) is a common cell surface ligand in animals which is not biosynthesized in humans but can be acquired in human tissue from dietary sources such as red meat. It is important to understand the relevance of this potentially immunogenic glycan on human health, and selective detection methods are needed that can disting...

Sialic acids are cell surface sugars present in many animal glycoproteins and are of particular interest in biopharmaceuticals, where lack of sialylation can reduce bioactivity. Here we describe how α-2,6-sialyltransferase from Photobacterium Damselae can be used to markedly increase sialylation of CHO produced alpha-1-antitrypsin. Detailed analysi...

Utilising a fast and sensitive screening method based on imidazolium tagged probes, we report unprecedented reversible activity of bacterial β1,4-galactosyltransferases to catalyse the transgalactosylation from lactose to N-acetylglucosamine to form...

Within human biology, combinations of regioisomeric motifs of α2,6- or α2,3-sialic acids linked to galactose are frequently observed attached to glycoconjugates. These include glycoproteins and glycolipids, with each linkage carrying distinct biological information and function. Microbial linkage-specific sialidases have become important tools for...

β(1,4)-Galactosyltransferase (β4Gal-T1) and T. cruzi trans-sialidase (TcTS) have been used in a ‘one-pot’ cascade to provide vesicles (liposomes) with a trisaccharide coating. These soluble enzymes catalysed the transfer of galactose then sialic acid onto a synthetic N-acetylglucolipid embedded in the bilayers. Clustering of this substrate into mic...

Glycosyl phosphates are important intermediates in many metabolic pathways and are substrates for diverse carbohydrate active enzymes. There is a need to develop libraries of structurally similar analogues that can be used as selective chemical probes in glycomics. Here we explore chemoenzymatic cascades for the fast generation of glycosyl phosphat...

This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, includi...

The cover picture shows how DNA-encoded libraries are becoming more widely employed by the academic, biotechnology and pharmaceutical communities for hit identification and target validation. Although significant progress has been made in expanding the toolkit of on-DNA compatible reactions, numerous synthetic transformations are still needed to in...

The identification of carbohydrate-protein interactions is central to our understanding of the roles of cell-surface carbohydrates (the glycocalyx), fundamental for cell-recognition events. Therefore there is a need for fast high-throughput biochemical tools to capture the complexity of these biological interactions. Here we describe a rapid method...

The increasing diversity of reactions mediated by biocatalysts has led to development of multi-step in vitro enzyme cascades, taking advantage of generally compatible reaction conditions. The construction of pathways within single whole cell systems is much less explored, yet has many advantages. Herein we report the generation of a successful whol...

DNA-encoded libraries are increasingly used for the discovery of bioactive lead compounds in high-throughput screening programmes against specific biological targets. Although a number of libraries are now available, they cover limited chemical space due to bias in ease of synthesis and the lack of chemical reactions that are compatible with DNA-ta...

p>In this manuscript we address an important gap in our current carbohydrate active enzyme toolbox, by developing a highly a2,6-selective (over a2,3-selective) de facto sialidase that is necessary both for glycan analysis and glycoconjugate remodeling. Both glycosidic linkages are commonly found in animal biology and each has been shown to have dis...

Enantiomerically pure chiral amines are ubiquitous chemical building blocks in bioactive pharmaceutical products and their synthesis from simple starting materials is of great interest. One of the most attractive strategies is the stereoselective installation of a chiral amine through CH amination, which is a challenging chemical transformation. H...

Enantiomerenreine, chirale Amine sind unentbehrliche Bausteine in bioaktiven Pharmazeutika, und ihre Synthese aus einfachen Startmaterialien ist daher von grosem Interesse. Eine der vielversprechendsten Strategien ist die chemisch anspruchsvolle, stereoselektive Synthese chiraler Amine durch eine C-H-Aminierung. Hier berichten wir uber den Einsatz...

Mass spectrometry is the primary analytical technique used to characterize the complex oligosaccharides that decorate cell surfaces. Monosaccharide building blocks are often simple epimers, which when combined produce diastereomeric glycoconjugates indistinguishable by mass spectrometry. Structure elucidation frequently relies on assumptions that b...

O-Mannosyl glycans are known to play an important role in regulating the function of α-dystroglycan (α-DG), as defective glycosylation is associated with various phenotypes of congenital muscular dystrophy. Despite the well-established biological significance of these glycans, questions regarding their precise molecular function remain unanswered....

Self-assembled monolayers (SAMs) on gold have become widely used as a platform for studying chemical and biochemical reactions, for studying biomolecular interactions and for the development of nanos-cale devices. We have used this platform to study the solid-supported synthesis of carbohydrates and glycopeptides using both chemical and enzymatic m...

Here, we present a comparative structure-function study of a nematode and a plant core α1,3-fucosyltransferase based on deletion and point mutations of the coding regions of Caenorhabditis elegans FUT-1 and Arabidopsis thaliana FucTA (FUT11). In particular, our results reveal a novel "first cluster motif" shared by both core and Lewis-type α1,3-fuc...

The vast majority of core structures of protein and peptide glycosylation motifs belong to either O-linked or N-linked glycans. A recent publication describes the structure and biosynthesis of an unusual S-linked glycan linkage in the antibacterial glycopeptide sublancin.

This work brings an insight on conserved motifs and sequence similarities of alpha1,3/4-fucosyltransferases with emphasis on plant core alpha1,3-fucosyltransferases. Core alpha1,3-fucosylation is a conserved feature of plant and invertebrate N-linked oligosaccharides with no yet known biological function. Core alpha1,3-fucosyltransferase activity i...

Ce travail cherche à apporter un éclairage sur les relations séquence-structure-fonction des alpha1,3/4-fucosyltransférases, avec un accent particulier sur les core alpha1,3-fucosyltransférases des plantes. La fucosylation de type Core alpha1,3 est une caractéristique des oligosaccharides N-liés des plantes et invertébrés, avec une fonction biologi...