Lipidated peptide synthesis

Abstract

AbstractIn this review, an overview is given for the synthesis of lipidated peptides such as those belonging to the Rab, Ras, eNOS, and hedgehog proteins. The different approaches for the synthesis of specific lipidated peptides (palmitoylated, prenylated, and myristoylated) are discussed with special emphasis on solid‐phase synthesis methods, because these methods have turned out to be the preferred synthesis method for most required peptides. Different solid‐phase methods are described that are individually suited for different types of lipidated peptides, differing, for example, in lipidation pattern or amino acid side‐chain functionality and in their protein ligation functionality. For the described solution approaches, the block coupling strategies followed for the different lipidated peptides are highlighted. A special section in this review discusses the different synthetic tools for the incorporation of the lipid functionalities in the peptides. Although a generally validated strategy for the synthesis of lipidated peptides does not exist, because of the large number of different functionalities, this review aids in the conceptual design of synthetic protocols for lipidated peptides. Finally, the methods for the ligation of lipidated peptides to proteins are shortly discussed, as these methods also significantly influence the design and synthesis of lipidated peptides.