Synthesis of Structural Analogues of Lyngbyatoxin A and Their Evaluation as Activators of Protein Kinase C

Alan P. Kozikowski, Patrick W. Shum, Alakananda Basu, John S. Lazo

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 languageEnglish
Pages (from-to)2420-2430
Number of pages11
JournalJournal of Medicinal Chemistry
Volume34
Issue number8
DOIs
StatePublished - 1 Aug 1991

Fingerprint

Protein Kinase C
Hydroxyl Radical
Histones
Thymus Gland
Carbon
Phosphorylation
Membranes
Enzymes
indolactam V
lyngbyatoxin A

Cite this

@article{36f279bfd9b4483cb92f026caa69e16f,
title = "Synthesis of Structural Analogues of Lyngbyatoxin A and Their Evaluation as Activators of Protein Kinase C",
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.",
author = "Kozikowski, {Alan P.} and Shum, {Patrick W.} and Alakananda Basu and Lazo, {John S.}",
year = "1991",
month = "8",
day = "1",
doi = "10.1021/jm00112a017",
language = "English",
volume = "34",
pages = "2420--2430",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "8",

}

Synthesis of Structural Analogues of Lyngbyatoxin A and Their Evaluation as Activators of Protein Kinase C. / Kozikowski, Alan P.; Shum, Patrick W.; Basu, Alakananda; Lazo, John S.

In: Journal of Medicinal Chemistry, Vol. 34, No. 8, 01.08.1991, p. 2420-2430.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis of Structural Analogues of Lyngbyatoxin A and Their Evaluation as Activators of Protein Kinase C

AU - Kozikowski, Alan P.

AU - Shum, Patrick W.

AU - Basu, Alakananda

AU - Lazo, John S.

PY - 1991/8/1

Y1 - 1991/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026077750&partnerID=8YFLogxK

U2 - 10.1021/jm00112a017

DO - 10.1021/jm00112a017

M3 - Article

C2 - 1875340

AN - SCOPUS:0026077750

VL - 34

SP - 2420

EP - 2430

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 8

ER -