Abstract
Adenosine diphosphate ribosylation (ADP-ribosylation) is a widely occurring post-translational modification of proteins at nucleophilic side chain of amino acid residues. Elucidation of ADP-ribosylation events would benefit greatly from the availability of well-defined ADP-ribosylated peptides and analogues thereof. In this paper we present a novel approach to the chemical synthesis of ribosylated amino acid building blocks using traceless Staudinger ligation. We describe an efficient and stereoselective synthesis of α-N-ribosyl-asparagine (α-N-ribosyl-Asn) and α-N-ribosyl-glutamine (α-N-ribosyl-Gln) building blocks starting from 5-tert-butyldiphenylsilyl-β-d-ribofuranosyl azide. The N-glycosyl aminoacids are produced in good yields as pure α-anomers, suitably protected for peptide synthesis.
Highlights
Glycosylated peptides play a fundamental role in biological systems: more than half of all proteins carry carbohydrate moieties, generating different glycoforms whose exact composition often controls protein function and distribution in biological systems [1,2,3,4]
One of the processes that is currently being elucidated is adenosine diphosphate ribosylation (ADP-ribosylation), a wide-occurring post-translational modification effected by enzymes that transfer ADP-ribose from NAD+ to Asn, Glu, Asp, Arg or Cys residues of proteins, so altering their function [7]
An important contribution for the clarification of the role of ADP-ribosylation events came in 2010, when Filippov and coworkers [8] reported the synthesis of ribosylated oligopeptides using α-N-ribosyl-asparagine (α-N-ribosyl-Asn) and α-N-ribosyl-glutamine (α-N-ribosylGln) building blocks
Summary
Glycosylated peptides play a fundamental role in biological systems: more than half of all proteins carry carbohydrate moieties, generating different glycoforms whose exact composition often controls protein function and distribution in biological systems [1,2,3,4]. The details of glycan regulation of protein activity and stability are still under intense scrutiny and the synthesis of well-defined glycopeptides is an important target [5,6], which still presents many challenges to organic. One of the processes that is currently being elucidated is adenosine diphosphate ribosylation (ADP-ribosylation), a wide-occurring post-translational modification effected by enzymes that transfer ADP-ribose from NAD+ to Asn, Glu, Asp, Arg or Cys residues of proteins, so altering their function [7]. An important contribution for the clarification of the role of ADP-ribosylation events came in 2010, when Filippov and coworkers [8] reported the synthesis of ribosylated oligopeptides using α-N-ribosyl-asparagine (α-N-ribosyl-Asn) and α-N-ribosyl-glutamine (α-N-ribosylGln) building blocks. Despite the relevance of this work, the approach suffers from a poorly selective synthesis of the required ribosylated building blocks 4α and 5α (Scheme 1), which were prepared by.
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