Design, synthesis, and biological evaluation of a potent, PKC selective, B-ring analog of bryostatin.
[structure: see text] The first member of a new class of five-membered B-ring analogs of bryostatin has been synthesized and tested for its ability to bind and translocate protein kinase C (PKC). This synthesis extends the utility of our previously introduced macrotransacetalization strategy to the formation of five-membered dioxolane B-ring analogs. This analog exhibits potent, single-digit nanomolar affinity to PKC and selectively translocates novel PKC isozymes.
Wender
Paul A
PA
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. wenderp@stanford.edu
Verma
Vishal A
VA
D000818:Animals; D054713:Bryostatins; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D054713:Bryostatins; D018942:Macrolides; C046785:bryostatin 1; D011493:Protein Kinase C