Synthesis of mono-ADP-ribosylated oligopeptides using ribosylated amino acid building blocks.
Adenosine diphosphate ribosylation (ADP-ribosylation) is a widely occurring post-translational modification of proteins at nucleophilic side chains of amino acid residues, such as asparagine, glutamic acid, and arginine. Elucidation of the biological role of ADP-ribosylation events would benefit from the availability of well-defined ADP-ribosylated peptides. Main issues in the construction of synthetic ADP-ribosylated peptides involve the availability of protected ribosylated amino acids suitable for peptide synthesis, development of a protective group strategy for peptide fragments compatible with the integrity of the adenosine diphosphate moiety, and an efficient procedure for pyrophosphate formation. In this paper we present a first approach to the chemical synthesis of ADP-ribosylated peptides in solution and on solid support. We describe an efficient synthesis of suitably protected ribosylated asparagine and glutamine building blocks suitable for Fmoc-based peptide synthesis. We further demonstrate a successful application of these ribosylated amino acids in the assembly of three fully synthetic ADP-ribosylated peptides by solution and solid phase approaches.
Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Gerbrand J
GJ
van der Heden van Noort
Maarten G
MG
van der Horst
Herman S
HS
Overkleeft
Gijsbert A
GA
van der Marel
Dmitri V
DV
Filippov
D000246:Adenosine Diphosphate Ribose / Q000138:chemical synthesis* / Q000737:chemistry; D001216:Asparagine / Q000737:chemistry*; D005973:Glutamine / Q000737:chemistry*; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D009842:Oligopeptides; D005973:Glutamine; D000246:Adenosine Diphosphate Ribose; D001216:Asparagine