How to Turn an Electron Transfer Protein into a Redox Enzyme for Biosensing

Cytochrome c is a small globular protein whose main physiological role is to shuttle electrons within the mitochondrial electron transport chain. This protein has been widely investigated, especially as a paradigmatic system for understanding the fundamental aspects of biological electron transfer and protein folding. Nevertheless, cytochrome c can also be endowed with a non-native catalytic activity and be immobilized on an electrode surface for the development of third generation biosensors. Here, an overview is offered of the most significant examples of such a functional transformation, carried out by either point mutation(s) or controlled unfolding. The latter can be induced chemically or upon protein immobilization on hydrophobic self-assembled monolayers. We critically discuss the potential held by these systems as core constituents of amperometric biosensors, along with the issues that need to be addressed to optimize their applicability and response.

Hemoglobin is also a murzyme mediating oxidative phosphorylation in human erythrocytes

Hemoglobin (Hb) transports oxygen via blood to various cells of the body and it is the most abundant protein found in erythrocytes. Herein, we propose an evidence-based hypothesis that Hb has a hitherto undiscovered function of serving as a murzyme (a redox enzyme working along the principles of murburn concept), catalyzing the synthesis of ATP in RBC, using diffusible reactive oxygen species (DROS). We support our hypothesis with theoretical arguments, earlier experimental findings and in silico explorations. The current work explains earlier reported in situ experimental findings/suggestions of 2,3-bisphosphoglycerate (BPG) and ADP binding at the same locus. We demonstrate that this interaction site is located at the heme cavity entrance with the binding energy in the order of BPG > NADH > ADP ~ ATP > AMP, thereby explaining important physiological outcomes. The findings pose significant implications in routine physiology and pathologies like sickle cell anemia and thalassemia.

Potential of Stimuli-Responsive Star Polymer for Cancer Targeting

Application of stimuli-responsive star polymers in cancer targeting and drug delivery has been extensively researched because of their several advantages in comparison with their linear counterparts. Functionalization and recombination of various arm architectures of the star polymer are very possible to be conducted to suit various needs. The star polymers could not only load more therapeutic drug due to more arms than linear polymers but also be functionalized with targeted moieties for more targeted delivery. Furthermore, the chains in star polymers could be regulated to produce stimuli-responsive star polymer for cancer targeting. The review article aimed to describe the benefits of star polymers and the types of stimuli-responsive delivery system for cancer targeting. Over the last decade, stimuli-responsive star polymers for cancer targeting using either internal stimuli (e.g., pH, redox, enzyme, hypoxia) or external stimuli (e.g., thermal, ultrasound, light, magnetic) has garnered immense interest for researchers. Possibility to mimic a complex natural phenomenon could be achieved by incorporating various stimuli-responsive functionalities in the star polymer.