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Deletion of the C26 Methyl Substituent from the Bryostatin Analogue Merle 23 Has Negligible Impact on Its Biological Profile and Potency
Author(s) -
Zhao Xiguang,
Kedei Noemi,
Michalowski Alexandra,
Lewin Nancy E.,
Keck Gary E.,
Blumberg Peter M.
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700677
Subject(s) - bryostatin 1 , potency , protein kinase c , biological activity , kinase , chemistry , stereochemistry , phorbol , substituent , biochemistry , in vitro , biology
Important strides are being made in understanding the effects of structural features of bryostatin 1, a candidate therapeutic agent for cancer and dementia, in conferring its potency toward protein kinase C and the unique spectrum of biological responses that it induces. A critical pharmacophoric element in bryostatin 1 is the secondary hydroxy group at the C26 position, with a corresponding primary hydroxy group playing an analogous role in binding of phorbol esters to protein kinase C. Herein, we describe the synthesis of a bryostatin homologue in which the C26 hydroxy group is primary, as it is in the phorbol esters, and show that its biological activity is almost indistinguishable from that of the corresponding compound with a secondary hydroxy group.