Nature-Inspired Radical Pyridoxal-Mediated C-C Bond Formation.

Pyridoxal-5'-phosphate (PLP) and derivatives of this cofactor enable a plethora of reactions in both enzyme-mediated and free-in-solution transformations. With few exceptions in each category, such chemistry has predominantly involved two-electron processes. This sometimes poses a significant challenge for using PLP to build tetrasubstituted carbon centers, especially when the reaction is reversible.

Simulating Electron Transfer Reactions in Solution: Radical-Polar Crossover.

Single-electron transfer (SET) promotes a wide variety of interesting chemical transformations, but modeling of SET requires a careful treatment of electronic and solvent effects to give meaningful insight. Therefore, a combined constrained density functional theory and molecular mechanics (CDFT/MM) tool is introduced specifically for SET-initiated reactions. Mechanisms for two radical-polar crossover reactions involving the organic electron donors tetrakis(dimethylamino)ethylene (TDAE) and tetrathiafulvalene (TTF) were studied with the new tool.

Chemoenzymatic -Quinone Methide Formation.

Generation of reactive intermediates and interception of these fleeting species under physiological conditions is a common strategy employed by Nature to build molecular complexity. However, selective formation of these species under mild conditions using classical synthetic techniques is an outstanding challenge. Here, we demonstrate the utility of biocatalysis in generating -quinone methide intermediates with precise chemoselectivity under mild, aqueous conditions.

A G Protein-Coupled Receptor Dimerization Interface in Human Cone Opsins.

G protein-coupled receptors (GPCRs) detect a wide variety of physical and chemical signals and transmit that information across the cellular plasma membrane. Dimerization is a proposed modulator of GPCR signaling, but the structure and stability of class A GPCR dimerization have been difficult to establish. Here we investigated the dimerization affinity and binding interface of human cone opsins, which initiate and sustain daytime color vision.

Class A Plexins Are Organized as Preformed Inactive Dimers on the Cell Surface.

Plexins are single-pass transmembrane receptors that bind the axon guidance molecules semaphorins. Single-pass transmembrane proteins are an important class of receptors that display a wide variety of activation mechanisms, often involving ligand-dependent dimerization or conformational changes. Resolving the activation mechanism and dimerization state of these receptors is extremely challenging, especially in a live-cell environment.