Alex Brogan

• PhD
• Senior Lecturer at King's College London

Single-enzyme catalysis offers a promising approach for unravelling the dynamic behaviour of individual enzymes as they undergo a reaction, revealing the complex heterogeneity that is lost in the averaged ensembles. Here we demonstrate real-time, label-free monitoring of the electrical transduction of single-protein enzymatic activity for two redox...

Viologens, 1,1′-disubstituted-4,4′-bipyridinium salts, are organic redox species that can be used in place of NADPH as mediators for redox enzymes. In this study, using the reduction of oxidized glutathione by glutathione reductase as a model system, a rationally designed library of viologens covering a range of polarities and functional groups wer...

Nucleic acid therapeutics have attracted recent attention as promising preventative solutions for a broad range of diseases. Nonviral delivery vectors, such as cationic polymers, improve the cellular uptake of nucleic acids without suffering the drawbacks of viral delivery vectors. However, these delivery systems are faced with a major challenge fo...

The accumulation of plastic waste in the environment is an ecological disaster that requires a plurality of approaches to tackle. There is therefore an ever-pressing need to close the loop on production of both conventional and bioderived plastics. In response, we propose a generalizable biocatalysis engineering strategy to enhance the use of enzym...

The cytochrome P450 family of enzymes have been shown to be powerful biocatalysts for a wide range of selective transformations. However, the industrial uptake of P450 enzymes has been low...

Protein-protein interactions are fundamental to life processes. Complementary computational, structural and biophysical studies of these interactions enable the forces behind their specificity and strength to be understood. Antibody fragments such as single-chain antibodies have the specificity and affinity of full antibodies but a fraction of thei...

Chemical modification of proteins to yield solvent-free liquid proteins has been demonstrated to be a robust method for stabilizing proteins against temperature, aggregation, and non-aqueous environments. This new class of biomaterial shows exceptional compatibility with ionic liquids, with enzyme architecture preserved and its activity enhanced. T...

The interaction between proteins and hydration water stabilizes protein structure and promotes functional dynamics, with water translational motions enabling protein flexibility. Engineered solvent-free protein-polymer hybrids have been shown to preserve protein structure, function, and dynamics. Here, we used neutron scattering, protein and polyme...

Ionogels are emerging as soft materials with remarkable physical properties that can be tuned to suite application requirements. The liquid component — ionic liquids — are effectively involatile, which provides new opportunities to explore gel surfaces with UHV based analytical techniques. Here, we exploit the highly solvating nature of ionic liqui...

The temperature sensitivity of vaccines and therapeutic proteins forces the distribution of life‐saving treatments to rely heavily on the temperature‐controlled (usually 2–8°C) supply and distribution network known as the cold chain. Here, using avidin as a model, we demonstrate how surface engineering could significantly increase the thermal stabi...

Ionic liquids offer exciting possibilities for biocatalysis as solvent properties provide rare opportunities for customizable, energy-efficient bioprocessing. Unfortunately, proteins and enzymes are generally unstable in ionic liquids and several attempts have been made to explain why; however, a comprehensive understanding of the ionic liquid–prot...

Ionogels are an emerging class of soft material with exceptional properties stemming from high ionic liquid content. In contrast to other gel systems, the ionic liquid component provides an extra level of design. However, this highly modular nature has yet to be fully explored and the role ionic liquids play in the structural properties of gel-base...

Here, we demonstrate a chemical modification strategy to create biomaterials of the M13 bacteriophage with extraordinary thermal stability, and high compatibility with non-aqueous ionic liquids. The results provide a blueprint...

The increasing requirement to produce platform chemicals and fuels from renewable sources means advances in biocatalysis are rapidly becoming a necessity. Biomass is widely used in nature as a source of energy and as chemical building blocks. However, recalcitrance towards traditional chemical processes and solvents provides a significant barrier t...

Nonaqueous biocatalysis is rapidly becoming a desirable tool for chemical and fuel synthesis in both the laboratory and in industry. Similarly, ionic liquids are an increasingly popular anhydrous reaction media for a number of industrial processes. Consequently, the use of enzymes in ionic liquids as efficient, environment-friendly, commercial bioc...

Solvent-free liquid proteins are a new class of thermally stable hybrid bionanomaterials that are produced by extensive lyophilisation of aqueous solutions of protein-polymer surfactant nano-conjugates followed by thermal anneal-ing. The hybrid constructs, which consist of a globular protein core surrounded by a monolayer of electrostatically cou-p...

Water molecules play a number of critical roles in enzyme catalysis, including mass transfer of substrates and products, nucleophilicity and proton transfer at the active site, and solvent shell-mediated dynamics for accessing catalytically competent conformations. The pervasiveness of water in enzymolysis therefore raises the question concerning w...

An anisotropic glucose oxidase-polymer surfactant nano-conjugate is synthesized and shown to exhibit complex temperature-dependent phase behavior in the solvent-free state. At close to room temperature, the nano-conjugate crystallizes as a mesolamellar soft solid with an expanded interlayer spacing of ca. 12 nm and interchain correlation lengths co...

Redox responses associated with the heme prosthetic group in a myoglobin-polymer surfactant solvent-free liquid are investigated for the first time in the absence of an electrolyte solution. Cyclic voltammograms from the biofluid exhibit responses that are consistent with planar diffusion of mobile charges in the melt. Temperature-dependent dynamic...

The thermal denaturation of solvent-free liquid lysozyme at temperatures in excess of 200°C was studied by synchrotron radiation circular dichroism spectroscopy. Temperature-dependent changes in secondary structure were used to map the equilibrium denaturation pathway and characterize a reactive β-sheet-rich unfolding intermediate that was stable i...

The observation of biological activity in solvent-free protein-polymer surfactant hybrids challenges the view of aqueous and nonaqueous solvents being unique promoters of protein dynamics linked to function. Here, we combine elastic incoherent neutron scattering and specific deuterium labeling to separately study protein and polymer motions in solv...

Isolating solvent effects by studying proteins in a liquid phase devoid of solvent has not been previously possible because freeze-dried protein solids do not melt but thermally degrade. Herein we circumvent this problem by modifying the interactions between myoglobin molecules via a polymer-surfactant coronal layer to produce a solvent-free liquid...

The ensemble of forces that stabilize protein structure and facilitate biological function are intimately linked with the ubiquitous aqueous environment of living systems. As a consequence, biomolecular activity is highly sensitive to the interplay of solvent-protein interactions, and deviation from the native conditions, for example by exposure to...