Frustrated, or nonoptimal, interactions have been proposed to be essential to a protein's ability to display responsive behavior such as allostery, conformational signaling, and signal transduction. However, the intentional incorporation of frustrated noncovalent interactions has not been explored as a design element in the field of dynamic foldamers. Here, we report the design, synthesis, characterization, and molecular dynamics simulations of the first dynamic water-soluble foldamer that, in response to a stimulus, exploits relief of frustration in its noncovalent network to structurally rearrange from a pleated to an intercalated columnar structure.
View Article and Find Full Text PDFProtein kinase A (PKA) is a biologically important enzyme for cell regulation, often referred to as the "central kinase". An immobilized PKA that retains substrate specificity and activity would be a useful tool for laboratory scientists, enabling targeted phosphorylation without interference from downstream kinase contamination or kinase autophosphorylation in sensitive assays. Moreover, it might also provide the benefits of robustness and reusability that are often associated with immobilized enzyme preparations.
View Article and Find Full Text PDFProteases with highly specific activities have numerous applications, including the cleavage of affinity tags (Flag; HA; His6X) and solubility promoting partners (GST; MBP) within the context of protein isolation and purification schemes. However, commercially sourced proteases such as Tobacco Etch Virus protease (TEVp) and Human Rhinovirus (HRV) 3C protease are typically applied as single use aliquots, which limits their cost-effectiveness. In addition, the presence of residual proteases in downstream applications can complicate analysis of the protein of interest.
View Article and Find Full Text PDFPhenols are attractive starting materials for the preparation of highly substituted cyclohexane rings via dearomative processes. Herein we report an efficient preparation of dearomatized 1-oxaspiro[2.5]octa-4,7-dien-6-ones (-spiroepoxydienones) via the nucleophilic epoxidation of in situ generated -quinone methides from 4-(hydroxymethyl)phenols using aqueous HO.
View Article and Find Full Text PDFWe present the case of an ultra-marathon runner who developed a painful irritated eye due to prolonged exposure to high wind speed and sub-zero temperatures causing transient freezing and subsequent abrasion of the cornea. We recommend that all ultra-marathon runners racing in windy or exposed conditions should wear wrap-around eye protection or goggles. If runners present to checkpoints or after the race to primary care or the emergency department with ocular pain, corneal freezing and abrasions should be considered.
View Article and Find Full Text PDFUpper limb injuries are a common occurrence in snowboarders, and these may be reduced by wearing wrist guards that transmit the force of the fall across the forearm. We present a case of a 26-year-old man who experienced a displaced left radial and ulnar fracture related to wearing a wristwatch while snowboarding. The wristwatch acted as a fulcrum around which the arm was fractured, serving as a stress riser that focused the force of the fall.
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