Effect of Bioconjugation on the Reduction Potential of Heme Proteins

The modification of protein surfaces employing cationic and anionic species enables the assembly of these biomaterials into highly sophisticated hierarchical structures. Such modifications can allow bioconjugates to retain or amplify their functionalities under conditions in which their native structure would be severely compromised. In this work, we assess the effect of this type of bioconjugation on the redox properties of two model heme proteins, that is, cytochrome c (CytC) and myoglobin (Mb). In particular, the work focuses on the sequential modification by 3-dimethylamino propylamine (DMAPA) and 4-nonylphenyl 3-sulfopropyl ether (S1) anionic surfactant. Bioconjugation with DMAPA and S1 are the initial steps in the generation of pure liquid proteins, which remain active in the absence of water and up to temperatures above 150 °C. Thin-layer spectroelectrochemistry reveals that DMAPA cationization leads to a distribution of bioconjugate structures featuring reduction potentials shifted up to 380 mV more negative than the native proteins. Analysis based on circular dichroism, MALDI-TOF mass spectrometry, and zeta potential measurements suggest that the shift in the reduction potentials are not linked to protein denaturation, but to changes in the spin state of the heme. These alterations of the spin states originate from subtle structural changes induced by DMAPA attachment. Interestingly, electrostatic coupling of anionic surfactant S1 shifts the reduction potential closer to that of the native protein, demonstrating that the modifications of the heme electronic configuration are linked to surface charges

Enhancing active surveillance of prostate cancer: the potential of exercise medicine

Active surveillance (AS) is a strategy for the management of patients with low-risk, localized prostate cancer, in which men undergo regular monitoring of serum PSA levels and tumour characteristics, using multiparametric MRI and repeat biopsy sampling, to identify signs of disease progression. This strategy reduces overtreatment of clinically insignificant disease while also preserving opportunities for curative therapy in patients whose disease progresses. Preliminary studies of lifestyle interventions involving basic exercise advice have indicated that exercise reduces the numbers of patients undergoing active treatment, as well as modulating the biological processes involved in tumour progression. Therefore, preliminary evidence suggests that lifestyle and/or exercise interventions might have therapeutic potential in this growing population of men with prostate cancer. However, several important issues remain unclear: the exact value of different types of lifestyle and exercise medicine interventions during AS; the biological mechanisms of exercise in delaying disease progression; and the influence of the anxieties and distress created by having a diagnosis of cancer without then receiving active treatment. Future studies are required to confirm and expand these findings and determine the relative contributions of each lifestyle component to specific end points and patient outcomes during AS