Inhibition of octapeptide N-myristoylation by acyl amino acids and acyl alkanolamines.
Several acyl amino acids and acyl alkanolamines were prepared and screened for their inhibition of octapeptide N-myristoylation and HIV-1 replication in MT-4 cells. Of the 62 acyl derivatives tested, N-myristoyl-O-caproyl-L-serine, N-myristoyl-O-caproyl-D-serine and N-decanoyl-O-myristoyl-L-serine were found to be uncompetitive inhibitors of N-myristoylation, but did not prevent HIV-induced cytopathicity in MT-4 cells. However, other acyl derivatives such as N-3-hydroxymyristoyl ethanolamine, N-3-hydroxymyristoyl-D-serine and N-myristoyl-L-cysteine, which did not inhibit N-myristoylation, suppressed the cytopathicity in the infected cells. The acyl derivatives described here may serve as lead compounds for antiviral agents.
Tabuchi
M
M
Department of Bioapplied Chemistry, Osaka City University, Japan.
Okamoto
H
H
Furutani
T
T
Azuma
M
M
Ooshima
H
H
Otake
T
T
Kawahata
T
T
Kato
J
J
D000215:Acylation / Q000187:drug effects; D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology*; D000605:Amino Alcohols / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D007700:Kinetics; D009226:Myristates / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D009842:Oligopeptides / Q000378:metabolism*; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology
D000596:Amino Acids; D000605:Amino Alcohols; D019380:Anti-HIV Agents; D005227:Fatty Acids; D009226:Myristates; D009842:Oligopeptides; D012694:Serine; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; D003066:Coenzyme A Ligases; C079990:myristoyl-CoA synthetase; D003545:Cysteine