Synthetic Lectins for Oligosaccharide Binding in Aqueous Media

Lead Research Organisation: University of Bristol
Department Name: Chemistry

Abstract

Synthetic receptors can help to throw light on the processes of life by mimicking the interactions between biomolecules. The binding of carbohydrates is especially mysterious, and especially difficult to reproduce under natural (aqueous) conditions. We have recently demonstrated the first well-authenticated receptor for the common monosaccharides in water. Our design may be likened to a classical temple, in which roof, floor and pillars make contact with matching portions of the carbohydrate. We have also studied a longer analogue ( extended-temple ) designed to bind disaccharides in (less challenging) organic media. This latter compound shows extraordinary selectivity for just one disaccharide substrate.We now plan to make receptors which will bind di- and oligosaccharides in water - the first molecules to be specifically designed for this purpose. The receptors are likely to show high affinities, perhaps comparable with some carbohydrate-binding proteins (lectins). They should also show good selectivities for particular disaccharide units which are found in plant, fungal and bacterial cell walls. We will use them to study the driving forces for natural carbohydrate binding, for example by varying their structures and the medium in which they operate. We will also develop versions which can be applied in biological research. One aim is to highlight the target disaccharides in developing cell walls, using fluorescent analogues of the receptors. Another is to interrupt cell wall synthesis, perhaps leading to antimicrobial agents. If we succeed we will have demonstrated, for the first time, that biomimetic carbohydrate receptors can be useful in a biological context.

Publications

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Barwell NP (2009) A synthetic lectin for beta-glucosyl. in Angewandte Chemie (International ed. in English)

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Davis AP (2009) Synthetic lectins. in Organic & biomolecular chemistry

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Ferrand Y (2007) A synthetic lectin analog for biomimetic disaccharide recognition. in Science (New York, N.Y.)

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Ferrand Y (2009) A synthetic lectin for O-linked beta-N-acetylglucosamine. in Angewandte Chemie (International ed. in English)

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Howgego JD (2013) An accessible bicyclic architecture for synthetic lectins. in Chemical communications (Cambridge, England)

 
Description We have shown that certain disaccharides, especially the cellulose fragment cellobiose, can be bound quite strongly and very selectively by synthetic receptors in water. The receptors were designed to mimic natural carbohydrate receptors (lectins), in that they use only non-covalent interactions. In practice they came quite close to matching the performance of some of these proteins, justifying the label "synthetic lectins".
Exploitation Route Synthetic lectins could find various applications in the biomedical sciences (e.g. diagnostics, novel pharmaceuticals) if sufficiently effective. Specific applications of oligosaccharide receptors lie in the areas of antibacterial or antifungal agents, and also in the utilisation of polysaccharide biomaterials.
Sectors Chemicals,Environment,Healthcare,Manufacturing, including Industrial Biotechology

 
Description This programme has continued through a succeeding EPSRC grant which has resulted in improved designs, including a molecule which can bind extended oligosaccharide chains. More development is required, but we may now be within reach of molecules with potential for biological activity, or might be used to help modify polysaccharide biomaterials.
 
Description EPSRC standard grant
Amount £328,370 (GBP)
Funding ID EP/I028501/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 10/2011 
End 10/2014
 
Description Marie Curie Fellowship
Amount € 181,103 (EUR)
Funding ID PIEF-GA-2009-252395 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 05/2010 
End 04/2012
 
Description Newton Fellowship
Amount £66,000 (GBP)
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2009 
End 08/2011
 
Title Implantable Blood Glucose Monitoring Devices 
Description  
IP Reference GB0912971.9 
Protection Patent application published
Year Protection Granted
Licensed No
 
Company Name Ziylo 
Description Ziylo is being established to commercialise the application of synthetic lectins in carbohydrate sensors 
Year Established 2014 
Impact x