Synthesis of Mono-ADP-Ribosylated Oligopeptides Using Ribosylated Amino Acid Building Blocks

摘要

Abstract: Adenosine diphosphate ribosylation (ADP-ribosylation) is a widely occurring post-translationalnmodification of proteins at nucleophilic side chains of amino acid residues, such as asparagine, glutamicnacid, and arginine. Elucidation of the biological role of ADP-ribosylation events would benefit from thenavailability of well-defined ADP-ribosylated peptides. Main issues in the construction of synthetic ADP-nribosylated peptides involve the availability of protected ribosylated amino acids suitable for peptide synthesis,ndevelopment of a protective group strategy for peptide fragments compatible with the integrity of thenadenosine diphosphate moiety, and an efficient procedure for pyrophosphate formation. In this paper wenpresent a first approach to the chemical synthesis of ADP-ribosylated peptides in solution and on solidnsupport. We describe an efficient synthesis of suitably protected ribosylated asparagine and glutaminenbuilding blocks suitable for Fmoc-based peptide synthesis. We further demonstrate a successful applicationnof these ribosylated amino acids in the assembly of three fully synthetic ADP-ribosylated peptides by solutionnand solid phase approaches.