Membrane localization and function of many signal proteins in higher eukaryotes are dependent on their covalent modification by specific lipids. However, because of the acid- and base-lability of lipoproteins, the synthesis of protein conjugates is severely complicated. Inthis paper, we review novel strategies to synthesize lipid-modified proteins,involving the bacterial expression of a carboxy-terminal truncated non-lipidated proteins and the chemical synthesis of differently lipidated peptides representing the C-terminus of the proteins and their covalent coupling. As representative lipoproteins, Ras-derived peptides and fully functional Ras proteins containing different lipid modification can efficiently be synthesized by the bioorganic method that combines the use of enzymatic protecting group with the technique of noble-metal catalyzed removal of blocking functions. These compounds used in cell biological experiment exhibit properties which are very similar to fully processed Ras open for selective modifications, which can be produced in highyields. The development of methods for the synthesis of lipoproteins will benefit the research of signal transduction and oncogenic variants in organism. The chemical synthesis and biological application of lipoproteins have crossed thebarrier and bridge the undoubted gap in research culture between chemistry andbiology, leading to new stimuli for chemical-biological research.

Key words: lipoprotein, signal transduction, Ras protein, lipid modification