Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation.

Mutations at a highly conserved homologous residue in three closely related muscle myosins cause three distinct diseases involving muscle defects: R671C in β-cardiac myosin causes hypertrophic cardiomyopathy, R672C and R672H in embryonic skeletal myosin cause Freeman-Sheldon syndrome, and R674Q in perinatal skeletal myosin causes trismus-pseudocamptodactyly syndrome. It is not known whether their effects at the molecular level are similar to one another or correlate with disease phenotype and severity. To this end, we investigated the effects of the homologous mutations on key factors of molecular power production using recombinantly expressed human β, embryonic, and perinatal myosin subfragment-1.

Homologous mutations in , embryonic, and perinatal muscle myosins have divergent effects on molecular power generation.

Mutations at a highly conserved homologous residue in three closely related muscle myosins cause three distinct diseases involving muscle defects: R671C in -cardiac myosin causes hypertrophic cardiomyopathy, R672C and R672H in embryonic skeletal myosin cause Freeman Sheldon syndrome, and R674Q in perinatal skeletal myosin causes trismus-pseudocamptodactyly syndrome. It is not known if their effects at the molecular level are similar to one another or correlate with disease phenotype and severity. To this end, we investigated the effects of the homologous mutations on key factors of molecular power production using recombinantly expressed human , embryonic, and perinatal myosin subfragment-1.

Exploiting the sp character of bicyclo[1.1.1]pentyl radicals in the transition-metal-free multi-component difunctionalization of [1.1.1]propellane.

Strained bicyclic substructures are increasingly relevant in medicinal chemistry discovery research because of their role as bioisosteres. Over the last decade, the successful use of bicyclo[1.1.

Selectivity in the Elaboration of Bicyclic Borazarenes.

Among aromatic compounds, borazarenes represent a significant class of isosteres in which carbon-carbon bonds have been replaced by B-N bonds. Described herein is a summary of the selective reactions that have been developed for known systems, as well as a summary of computationally-based predictions of selectivities that might be anticipated in reactions of yet unrealized substructures.