Solid-phase synthesis of prenylcysteine analogs.
Prenylcysteine derivatives are of interest for a variety of different biological reasons, including probing the CaaX protein processing pathway. A solid-phase synthesis protocol for the preparation of prenylcysteines using 2-chlorotrityl chloride resin as a solid support has been developed. A series of novel amide-modified farnesylcysteine analogs were synthesized in both high purity and yield under mild conditions. The farnesylcysteine analogs were evaluated using human isoprenylcysteine carboxyl methyltransferase as a biological target, and several new inhibitors, one with significantly enhanced potency, were identified.
Donelson
James L
JL
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA.
Hodges-Loaiza
Heather B
HB
Henriksen
Brian S
BS
Hrycyna
Christine A
CA
Gibbs
Richard A
RA