s-farnesylcysteine and prenylcysteine

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.

Topics: Amino Acid Sequence; Chromatography, High Pressure Liquid; Cysteine; Humans; Molecular Structure; Protein Methyltransferases; Solid Phase Extraction; Trityl Compounds