David J. Page

Direct electrochemistry, at modified gold electrodes, of redox proteins having negatively-charged binding domains: spinach plastocyanin and a multi-substituted carboxydinitrophenyl derivative of horse heart cytochrome c

Abstract The direct electrochemistry of spinach plastocyanin and a multi-substituted carboxydinitrophenyl (CDNP) derivative of horse heart cytochrome c at gold electrodes modified with 2-aminoethanethiol, 2,2′-dithiobisethanamine and (pyridinylmethylene)hydrazinecarbothioamides, is described. A comparison is made with the electrochemistry of native horse heart cytochrome c . The results are interpreted in terms of interaction of negatively-charged binding domains on the surface of plastocyanin and the multi-CDNP cytochrome c with the modified electrode surface.

Surface substitution reactions at modified gold electrodes and their effect on the electrochemistry of horse heart cytochrome c

Abstract The direct electrochemistry of horse heart cytochrome c has been used to investigate surface substitution reactions proceedings at gold electrodes initially pre-modified by a single species. Two aspects of these investigations are described. The first concerns the effect of poly-L-lysine on pre-adsorbed monolayers of surface-modifiers. The modifier 1,2-bis(4-pyridyl)ethylene is found to be displaced by even low RMM poly-lysine while bis(4-pyridyl)bisulphide is resistant to such displacement. The latter is, however, easily displaced by high RMM poly-lysine although another modifier, PATS-4, is resistant even to this. The second aspect of the investigations described concerns experiments in which an initially intact adsorbed layer of one surface modifier is displayed progressively, with time, by a second surface modifier. It is suggested that analysis of the results of some of these experiments gives a useful insight into the mechanism of the cytochrome c electrode reaction.

Direct electrochemistry of bacterial cytochrome c551 at surface-modified gold electrodes

Abstract The direct electrochemistry of the single heme cytochrome c 551 from the bacterium Pseudomonas aeruginosa has been investigated at gold electrodes surface-modified through chemisorption of polyfunctional organic molecules. The results have been compared and contrasted with those obtained under the same conditions for the eukaryotic cytochrome c from horse heart. Both cytochromes give a quasi-reversible electrode reaction at pH 6.0 at a modified interface presenting only 4-pyridyl groups to the solution suggesting the occurrence, in both cases, of a hydrogen bonding interaction from lysine side-chains on the protein to pyridyl-nitrogens on the electrode surface. However, in contrast, gold electrodes modified by Pyridine- n -AldehydeThioSemicarbazones ( n = 2, 3, 4) give electrochemistry which is strongly isomer-dependent in the case of horse heart cytochrome c but completely isomer-independent in the case of cytochrome c 551 . It is suggested that interaction of the eukaryotic protein with surfaces is dominated by its lysine residues only, but that interaction of the bacterial cytochrome is through hydrogen bonding from the surface to both lysines and carboxylate groups of aspartate residues. This is supported by observation of the loss of cytochrome c 551 electrochemistry at 4-pyridyl-only modified gold at pH 9.0 compared with the good, quasi-reversible electrochemistry maintained under the same conditions at PATS-4 modified gold. It is concluded that, while the two cytochromes show many similarities with respect to their structures and functions, they have quite different interfacial electron transfer reactions, particularly at PATS-modified electrodes. This may correlate with the known large differences between the two proteins in net electrostatic charge and surface charge distribution.

An Initial Experiment into Stereochemistry-Based Drug Design Using Inductive Logic Programming

Previous applications of Inductive Logic Programming to drug design have not addressed stereochemistry, or the three-dimensional aspects of molecules. While some success is possible without consideration of stereochemistry, researchers within the pharmaceutical industry consider stereochemistry to be central to most drug design problems. This paper reports on an experimental application of the ILP system P-Progol to stereochemistry-based drug design. The experiment tests whether P-Progol can identify the structure responsible for the activity of ACE (angiotensin-converting enzyme inhibitors from 28 positive examples, that is, from 28 molecules that display the activity of ACE inhibition. ACE inhibitors are a widely-used form of medication for the treatment of hypertension. It should be stressed that this structure was already known prior to the experiment and therefore is not a new discovery; the experiment was proposed by a researcher within the pharmaceutical industry to test the applicability of ILP to stereochemistry-based drug design. While the result of the experiment is quite positive, one challenge remains before ILP can be applied to a multitude of drug design problems.

The enzyme-catalysed electrochemical conversion of p-cresol into p-hydroxybenzaldehyde

The electrochemical oxidation of p-cresol was effected enzymically, using either a blue copper protein, azurin, or ferroceneboronic acid as the mediator of the anodic reaction, giving p-hydroxybenzaldehyde as the only product.

A spin labelled electrode

A spin label has been synthesised and used as a probe for the electrode–electrolyte interface, both in the presence and absence of a redox protein.