Designing polymers to tackle challenges in health and sustainability; A synthetic polymer scaffold for multivalent glycan-binding proteins

Dr Claire S Mahon Designing polymers to tackle challenges in health and sustainability Ben Fenton A synthetic polymer scaffold for multivalent glycan-binding proteins

Designing polymers to tackle challenges in health and sustainability

Dr Claire S Mahon, University of Durham

The versatility of synthetic polymers arises from our ability to control their chemical composition, architecture and functionality. This provides opportunities not only to engineer increasingly sophisticated materials, but also to reconsider how polymers interact with the biological systems they encounter. In the Mahon group, we apply synthetic polymer chemistry at the interface with biology, asking how molecular-level design can be used both to create new function and to minimise environmental impact. In this talk, I will present two examples of this approach: the development of polymer sensors capable of recognising changes in bacterial phenotype, and the redesign of polymers to mediate their environmental fate. Polymer sensors that recognise bacterial adaptation. Many bacterial pathogens can evolve and diversify within their hosts, producing phenotypic changes that contribute to persistent infections which can be challenging to identify using conventional diagnostic approaches. Pseudomonas aeruginosa, for example, undergoes extensive adaptation during chronic respiratory infections, including changes in surface phenotype, virulence and biofilm formation. I will describe a cross-reactive sensor array of fluorescent glycopolymer probes capable of discriminating P. aeruginosa from other respiratory pathogens and identifying phenotypic changes associated with the transition from acute to chronic infection.1 Designing polymers with improved sustainability profile. The environmental impact of a polymer is determined not only by its chemical structure, but the sourcing of its building blocks and the environment in which it ultimately resides. While considerable attention has been paid to the development of biosourced plastics, and their biodegradation under conditions such as industrial composting, much less is understood about the environmental impacts of the water soluble polymers used in everyday consumer products. I will describe our work towards redesigning polymers used in consumer goods to improve their sustainability profile.2, 3 By considering environmental impact alongside performance from the outset, we aim to establish approaches to polymer design that can reduce the environmental footprint of these widely used materials. BIOGRAPHY The Mahon group explore the interface between materials science and biological chemistry. By combining our expertise in synthetic polymer chemistry and biology, we develop new materials which can interact with biological systems to perform functions in the detection and capture of pathogens, or to provide new information about how biological recognition systems work. Concurrently, we develop sustainable new materials by exploring new avenues in polymer synthesis and controlled degradation. Clare was awarded her PhD at Newcastle University in 2014, where she worked with Dr David A. Fulton establishing new methods of ‘training’ synthetic polymers to recognise proteins and other macromolecules. She then spent two years at the University of Leeds on an EPSRC Doctoral Prize Fellowship, working with Prof. Bruce Turnbull to develop responsive synthetic polymers which interact with bacterial toxins. In 2017 she took up a Marie Skłodowska-Curie Global Fellowship, held at the University of Sydney, Australia, and the University of York, UK. During this time, Clare worked with Dr Elizabeth J. New and Dr Markus Müllner-Bačvić, focusing on applying differential sensing approaches to identify carbohydrate-binding proteins. In October 2019, Clare moved to Durham to start her own group as Assistant Professor in Synthetic Organic Chemistry.

A synthetic polymer scaffold for multivalent glycan-binding proteins

Ben Fenton, University of Leeds

Sialic acid, a glycan that decorates the surface of virtually all mammalian cells, is often overexpressed in cancer tissues. Targeting these glycans with conventional monovalent binders provides insufficient distinction between densities on healthy and diseased tissue. Our group has developed a method of using of multivalent displays of glycan-binding proteins conjugated along a polymer backbone. These materials can discriminate between surfaces with target glycans above and below a threshold density. While natural biopolymers can be used as scaffolds for binding proteins, they risk having intrinsic biological activities and degradation pathways. Here, a synthetic protocol using ring-opening metathesis polymerisation produces a poly(oxanorbornene imide) backbone with a defined valency and length, to which glycan-binding proteins are grafted in a 'plug-and-play' manner. The binding responses of this probe were measured on model cell surfaces that present target glycans at defined densities, showing selectivity superior to that of a monovalent binder. These results suggest that the probe may be suitable for the detection of cell surface glycans at higher densities than those in the surrounding tissue/organism.