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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.

ABSTRACT: 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.

SUBMITTER: Zhao X

PROVIDER: S-EPMC7032040 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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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.

Zhao Xiguang X Kedei Noemi N Michalowski Alexandra A Lewin Nancy E NE Keck Gary E GE Blumberg Peter M PM

Chembiochem : a European journal of chemical biology 20180427 10

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, ...[more]

PMID: 29517836

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The synthetic bryostatin analog Merle 23 dissects distinct mechanisms of bryostatin activity in the LNCaP human prostate cancer cell line.

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Robert Merle d'Aubigne, 1900-1989.

Project description: Not available

| S-EPMC2600977 | biostudies-literature

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| S-EPMC4183620 | biostudies-literature

Synthesis of seco-B-ring bryostatin analogue WN-1 via C-C bond-forming hydrogenation: critical contribution of the B-ring in determining bryostatin-like and phorbol 12-myristate 13-acetate-like properties.

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Fluorescent properties of DNA base analogue tC upon incorporation into DNA--negligible influence of neighbouring bases on fluorescence quantum yield.

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| S-EPMC1201328 | biostudies-literature

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