Protein prenylation is a post-translational modification of specific protein-derived cysteine residues critical for function in eukaryotic cells. Previous experiments with tetrapeptide sequences identified the motif known as the  CaaX box as the key structural element recognized by protein farnesyltransferase (PFTase). Here we describe the synthesis of peptides containing free C-termini on solid supports. A photocleavable linker was designed to release the peptides from the support and to allow their analysis by MS. Four types of solid supports (TentaGel, PEGA, CPG and cellulose membranes) were evaluated. MS results show that the cysteine-containing peptide can be prenylated while containing a cysteine to serine �mutation� cannot. This approach should allow a large number of C-terminal peptides to be screened as substrates for PFTase and for other enzymes involved in protein prenylation as well. Such experiments should help to define what C-terminal sequences make up the prenylome.

Preparation and analysis of peptide libraries with free C-termini for studying the prenylome

243rd National Meeting (2012)

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