Synthesis of palmitoylated Ras-peptides and -proteins

In this review, an overview is given and details are provided for the synthesis of lipidated Ras (rat-adeno-sarcoma)-peptides and -proteins. The progress made in the synthesis of the lipidated peptides from the Ras superfamily is discussed with special emphasis on the recently developed solid-phase synthesis methods, since these methods have turned out to be the preferred synthesis method for the majority of the required peptides. Solid-phase lipopeptide synthesis has given access to native and modified peptides on a scale that allows peptide-consuming studies like for ligation to proteins and concomitant X-ray crystal structure determination. The access to these peptides has also enabled biological questions concerning these peptides and proteins to be resolved. The review describes different solid-phase methods, which are individually suited for different types of lipopeptides, differing for example in lipidation pattern or amino acid side-chain functionality, and their ligation to proteins. Finally, an example is provided how these peptides can serve to resolve biological aspects of the Ras family GTPases. (c) 2006 Elsevier Inc. All rights reserved.