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Synthetic α- and β-Ser-ADP-ribosylated Peptides Reveal α-Ser-ADPr as the Native Epimer.

ABSTRACT: A solid-phase methodology to synthesize oligopeptides, specifically incorporating serine residues linked to ADP-ribose (ADPr), is presented. Through the synthesis of both α- and β-anomers of the phosphoribosylated Fmoc-Ser building block and their usage in our modified solid-phase peptide synthesis protocol, both α- and β-ADPr peptides from a naturally Ser-ADPr containing H2B sequence were obtained. With these, and by digestion studies using the human glycohydrolase, ARH3 (hARH3), compelling evidence is obtained that the α-Ser-ADPr linkage comprises the naturally occurring configuration.

SUBMITTER: Voorneveld J

PROVIDER: S-EPMC6038095 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Synthetic α- and β-Ser-ADP-ribosylated Peptides Reveal α-Ser-ADPr as the Native Epimer.

Voorneveld Jim J Rack Johannes G M JGM Ahel Ivan I Overkleeft Herman S HS van der Marel Gijsbert A GA Filippov Dmitri V DV

Organic letters 20180627 13

A solid-phase methodology to synthesize oligopeptides, specifically incorporating serine residues linked to ADP-ribose (ADPr), is presented. Through the synthesis of both α- and β-anomers of the phosphoribosylated Fmoc-Ser building block and their usage in our modified solid-phase peptide synthesis protocol, both α- and β-ADPr peptides from a naturally Ser-ADPr containing H2B sequence were obtained. With these, and by digestion studies using the human glycohydrolase, ARH3 (hARH3), compelling evi ...[more]

PMID: 29947522

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