RESUMEN
In large bicycloalkanes, several in/out forms exist, wherein substituents on the bridgehead atoms are oriented either outside or inside the cage. The relative stability between the in,out and twist-out,out forms, which can interconvert through homeomorphic conversion, was found to depend upon the cage size. The in,out form demonstrated thermodynamic stability in the smaller C10 derivative, whereas the twist-out,out form prevailed in the larger derivatives of C14 and C18 plausibly as a result of dispersion forces among the chains.
RESUMEN
Facile and simultaneous synthesis of diphenyl-disilabicyclo[14.14.14]alkane in/out-isomers was achieved by using organosilicon chemistry. Although the formation of several in/out-isomers would be conceivable, only two diastereomers, i.e. the (traditional-)out,out-isomer and the twist-out,out-isomer, could be isolated because of homeomorphic isomerization. Crystal structures of the diastereomers were confirmed.
RESUMEN
Horseshoe crab hemolymph coagulation is believed to be triggered by the autocatalytic activation of serine protease zymogen factor C to the active form, α-factor C, belonging to the trypsin family, through an active transition state of factor C responding to bacterial lipopolysaccharide (LPS), designated factor C*. However, the existence of factor C* is only speculative, and its proteolytic activity has not been validated. In addition, it remains unclear whether the proteolytic cleavage of the Phe737-Ile738 bond (Phe737 site) of factor C required for the conversion to α-factor C occurs intramolecularly or intermolecularly between the factor C molecules. Here we show that the Phe737 site of a catalytic Ser-deficient mutant of factor C is LPS-dependently hydrolyzed by a Phe737 site-uncleavable mutant, clearly indicating the existence of the active transition state of factor C without cleavage of the Phe737 site. Moreover, we found the following facts using several mutants of factor C: the autocatalytic cleavage of factor C occurs intermolecularly between factor C* molecules on the LPS surface; factor C* does not exhibit intrinsic chymotryptic activity against the Phe737 site, but it may recognize a three-dimensional structure around the cleavage site; and LPS is required not only to complete the substrate-binding site and oxyanion hole of factor C* by interacting with the N-terminal region but also to allow the Phe737 site to be cleaved by inducing a conformational change around the Phe737 site or by acting as a scaffold to induce specific protein-protein interactions between factor C* molecules.
Asunto(s)
Proteínas de Artrópodos/metabolismo , Precursores Enzimáticos/metabolismo , Cangrejos Herradura/enzimología , Lipopolisacáridos/metabolismo , Serina Endopeptidasas/metabolismo , Animales , Proteínas de Artrópodos/química , Dominio Catalítico , Activación Enzimática , Precursores Enzimáticos/química , Células HEK293 , Cangrejos Herradura/química , Cangrejos Herradura/metabolismo , Humanos , Conformación Proteica , Proteolisis , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Serina Endopeptidasas/químicaRESUMEN
An unprecedented catalytic C(sp(3))-H triborylation at a single carbon was developed with the assistance of a nitrogen directing group.