Contribution of the C1A and C1B domains to the membrane interaction of protein kinase C.

The hallmark for protein kinase C activation is its "translocation" to membranes following generation of lipid second messengers. This translocation is mediated by the C1 and C2 domains, two membrane-targeting modules, whose engagement on membranes provides the energy for an activating conformational change in which an autoinhibitory pseudosubstrate sequence is released from the active site. Novel and conventional protein kinase C isozymes contain a tandem repeat of C1 domains, the C1A and C1B, which each contain a binding pocket for phorbol esters/diacylglycerol.

Protein kinase C translocation by modified phorbol esters with functionalized lipophilic regions.

Several novel phorbol esters were prepared with polar functional groups terminating their C12 and/or C13 acyl chains. Designed to be inhibitory protein kinase C (PKC) ligands, these phorbol analogues contain various polar functional groups (amide, ester, carboxylic acid, or quaternary ammonium salt) to prevent membrane insertion of the PKC-phorbol ester complex. All phorbol derivatives were synthesized with use of diterpene starting materials obtained from croton oil, the seed oil of Croton tiglium.

Construction of [4.3.1]propellanes via molybdenum fischer carbene complexes.

Treatment of molybdenum Fischer carbene complexes with 6-methylene-7-octen-1-yne derivatives at 40 degrees C generates substituted tricyclo[4.3.1.