Abstract
Syntheses of several new analogues of lyngbyatoxin A from a single common intermediate are described. These compounds bear a carbon chain at the 7-position of the indolactam V (ILV) nucleus which contains either a hydrophilic or a lipophilic group. The effect of these minor structural alterations on the ability of the ILV analogues to activate the enzyme protein kinase C (PKC) was determined by measuring the extent of phosphorylation of calf thymus histone (III-S). Introduction of a hydroxyl group on the C-7 appendage was found to dramatically decrease compound 3’s ability to activate PKC. This result is interpreted in terms of the decreased ability of 3 to associate with the membrane bilayer.
Original language | English |
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Pages (from-to) | 2420-2430 |
Number of pages | 11 |
Journal | Journal of Medicinal Chemistry |
Volume | 34 |
Issue number | 8 |
DOIs | |
State | Published - 1 Aug 1991 |