Synthesis of desthio prenylcysteine analogs: sulfur is important for biological activity.
N-Acetyl-S-farnesyl cysteine (AFC) is the minimal synthetic substrate for the enzyme Icmt, which methylates prenylated proteins. The desthio-AFC isostere 2 has been synthesized in racemic form. This analog was not an Icmt substrate, but instead a weak inhibitor with an IC50 of approximately 325 microM.
Henriksen
Brian S
BS
Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Cancer Center, Purdue University, West Lafayette, IN 47907, USA.
Anderson
Jessica L
JL
Hrycyna
Christine A
CA
Gibbs
Richard A
RA
D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D020128:Inhibitory Concentration 50; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism
D013440:Sulfides; D013729:Terpenes; D008780:Methyltransferases; D003545:Cysteine