| Description |
Prenylation, a posttranslational modification that involves the formation of thioether bonds, is one of a series of reactions involved in converting Ras proteins into their active form. An overexpression of normal Ras protein has been linked to malignant transformation. Numerous prenylated proteins have been detected in mammalian cells and therefore new methods for the synthesis of prenylated proteins have stimulated considerable interest. In this project we have prepared and studied synthetic methods to generate prenylated peptides. First, the hydroxyl of serine can be replaced with a good leaving group which can be displaced by a nucleophile such as farnesyl thiol. This method results in isomers of the prenylated product. Farnesyl thiol, which is considered to be a good leaving group is generated from famesol. Another method involving the serine first being converted to a p-Iactone, was more; successful. Via the p-Iactone intermediate we were able to obtain the desired pure product; by having famesyl thiol attack the p-carbon to release the ring strain. Finally, a synthetic method was developed to synthesize dipeptides. These methods can also be used to synthesize prenylated polypeptides which may be used for further studies in developing inhibitors as potential anticancer agents. |
