The bryostatin 1 A-ring acetate is not the critical determinant for antagonism of phorbol ester-induced biological responses.
The contribution of the A-ring C(7) acetate to the function of bryostatin 1 has been investigated through synthesis and biological evaluation of an analogue incorporating this feature into the bryopyran core structure. No enhanced binding affinity for protein kinase C (PKC) was observed, relative to previously characterized analogues lacking the C(7) acetate. Functional assays showed biological responses characteristic of those induced by the phorbol ester PMA and distinctly different from those observed with bryostatin 1.
University of Utah, Department of Chemistry, Salt Lake City, Utah 84112, USA. keck@chemistry.utah.edu
Gary E
GE
Keck
Wei
W
Li
Matthew B
MB
Kraft
Noemi
N
Kedei
Nancy E
NE
Lewin
Peter M
PM
Blumberg
D054713:Bryostatins / Q000737:chemistry* / Q000494:pharmacology*; D003500:Cyclization; D015394:Molecular Structure; D011493:Protein Kinase C / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000737:chemistry / Q000494:pharmacology*
D054713:Bryostatins; C046785:bryostatin 1; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate