Advertisement

ADPr-Peptide Synthesis

  • Hans A. V. Kistemaker
  • Jim Voorneveld
  • Dmitri V. Filippov
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1813)

Abstract

Synthetic mono-ADPr-peptides are useful for structural, biochemical, and proteomics studies. We describe here a protocol for the preparation of mono-ADPr-peptides based on a fairly standard Fmoc-based solid-phase synthesis. Phosphoribosylated precursor building blocks are introduced into the peptide chain on solid-phase and subsequently converted to ADPr-sites by chemical phosphorylation with adenosine phosphoramidite. Suitably protected phosphoribosylated glutamine, asparagine, and citrulline building blocks described in this protocol allow introduction of ADP-Gln, ADPr-Asn, and ADPr-Cit into peptide chains as demonstrated for three peptides. Trifunctional amino acids, for which base-sensitive side-chain protection is available, can be accommodated in the sequences flanking the ADPr-cites.

Key words

Mono-ADPr-peptides Solid-phase synthesis Pyrophosphate Glycosylation Phosphitylation Phosphoribosylated amino acids 

Abbreviations

ACN

Acetonitrile

AcOH

Acetic acid

CSO

(1S)-(+)-(10-camphorsulfonyl)-oxaziridine

DBU

1,8-diazabicycloundec-7-ene

DCM

Dichloromethane

DiPEA

Diisopropylethylamine

Dmab

4-(N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino) benzyl ester

DMF

Dimethylformamide

Et2O

Diethyl ether

EtOH

Ethanol

HCTU

O-(1H-6-Chlorobenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate

HFIP

1,1,1,3,3,3-hexafluoro-2-propanol

NMP

N-methylpyrrolidone

TBDPS

tert-butyldiphenylsilyl

TBSOTf

tert-butyldimethylsilyl triflate

TEA

Triethylamine

Tfa

Trifluroacetamide (protective group)

TFA

Trifluoroacetic acid

Notes

Acknowledgments

This work was supported by the Netherlands Organization for Scientific Research (NWO).

References

  1. 1.
    Gupte R, Liu Z, Kraus WL (2017) PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes. Genes Dev 31(2):101–126. https://doi.org/10.1101/gad.291518.116 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ryu KW, Kim DS, Kraus WL (2015) New facets in the regulation of gene expression by ADP-ribosylation and poly(ADP-ribose) polymerases. Chem Rev 115(6):2453–2481. https://doi.org/10.1021/cr5004248 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Hassa PO, Haenni SS, Elser M, Hottiger MO (2006) Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev 70(3):789–829. https://doi.org/10.1128/Mmbr.00040-05 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Vyas S, Chesarone-Cataldo M, Todorova T, Huang YH, Chang P (2013) A systematic analysis of the PARP protein family identifies new functions critical for cell physiology. Nat Commun 4:2240. https://doi.org/10.1038/ncomms3240 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kistemaker HA, Nardozza AP, Overkleeft HS, van der Marel GA, Ladurner AG, Filippov DV (2016) Synthesis and macrodomain binding of mono-ADP-ribosylated peptides. Angew Chem Int Ed Engl 55(36):10634–10638. https://doi.org/10.1002/anie.201604058 CrossRefPubMedGoogle Scholar
  6. 6.
    Bilan V, Selevsek N, Kistemaker HA, Abplanalp J, Feurer R, Filippov DV, Hottiger MO (2017) New quantitative mass spectrometry approaches reveal different ADP-ribosylation phases dependent on the levels of oxidative stress. Mol Cell Proteomics 16(5):949–958. https://doi.org/10.1074/mcp.O116.065623 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Daniels CM, Ong SE, Leung AK (2015) The promise of proteomics for the study of ADP-ribosylation. Mol Cell 58(6):911–924. https://doi.org/10.1016/j.molcel.2015.06.012 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Laing S, Unger M, Koch-Nolte F, Haag F (2011) ADP-ribosylation of arginine. Amino Acids 41(2):257–269. https://doi.org/10.1007/S00726-010-0676-2 CrossRefPubMedGoogle Scholar
  9. 9.
    Kistemaker HAV, van der Heden van Noort GJ, Overkleeft HS, van der Marel GA, Filippov DV (2013) Stereoselective ribosylation of amino acids. Org Lett 15(9):2306–2309. https://doi.org/10.1021/Ol400929c CrossRefPubMedGoogle Scholar
  10. 10.
    van der Heden van Noort GJ, van der Horst MG, Overkleeft HS, van der Marel GA, Filippov DV (2010) Synthesis of mono-ADP-ribosylated oligopeptides using ribosylated amino acid building blocks. J Am Chem Soc 132(14):5236–5240. https://doi.org/10.1021/Ja910940q CrossRefPubMedGoogle Scholar
  11. 11.
    Gold H, van Delft P, Meeuwenoord N, Codee JDC, Filippov DV, Eggink G, Overkleeft HS, van der Marel GA (2008) Synthesis of sugar nucleotides by application of phosphoramidites. J Org Chem 73(23):9458–9460. https://doi.org/10.1021/jo802021t CrossRefPubMedGoogle Scholar
  12. 12.
    Kistemaker HAV, Lameijer LN, Meeuwenoord NJ, Overkleeft HS, van der Marel GA, Filippov DV (2015) Synthesis of well-defined adenosine diphosphate ribose oligomers. Angew Chem Int Ed Engl 54(16):4915–4918. https://doi.org/10.1002/anie.201412283 CrossRefPubMedGoogle Scholar
  13. 13.
    Kistemaker HAV, Meeuwenoord NJ, Overkleeft HS, van der Marel GA, Filippov DV (2015) On the synthesis of oligonucleotides interconnected through pyrophosphate linkages. Eur J Org Chem 2015(27):6084–6091. https://doi.org/10.1002/ejoc.201500911 CrossRefGoogle Scholar
  14. 14.
    Cremosnik GS, Hofer A, Jessen HJ (2014) Iterative synthesis of nucleoside oligophosphates with phosphoramidites. Angew Chem Int Ed Engl 53(1):286–289. https://doi.org/10.1002/Anie.201306265 CrossRefPubMedGoogle Scholar
  15. 15.
    Conroy T, Jolliffe KA, Payne RJ (2009) Efficient use of the Dmab protecting group: applications for the solid-phase synthesis of N-linked glycopeptides. Org Biomol Chem 7(11):2255–2258. https://doi.org/10.1039/b821051a CrossRefPubMedGoogle Scholar
  16. 16.
    Bonfiglio JJ, Fontana P, Zhang Q, Colby T, Gibbs-Seymour I, Atanassov I, Bartlett E, Zaja R, Ahel I, Matic I (2017) Serine ADP-ribosylation depends on HPF1. Mol Cell 65(5):932–940 e936. https://doi.org/10.1016/j.molcel.2017.01.003 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kistemaker HAV, Meeuwenoord NJ, Overkleeft HS, van der Marel GA, Filippov DV (2016) Solid-phase synthesis of oligo-ADP-ribose. Curr Protoc Nucl Acid Chem 64:4.68.61–64.68.27. https://doi.org/10.1002/0471142700.nc0468s64 CrossRefGoogle Scholar
  18. 18.
    van der Heden van Noort GJ, Verhagen CP, van der Horst MG, Overkleeft HS, van der Marel GA, Filippov DV (2008) A versatile one-pot procedure to phosphate monoesters and pyrophosphates using Di(p-methoxybenzyl)-N,N-diisopropylphosphoramidite. Org Lett 10(20):4461–4464. https://doi.org/10.1021/Ol801608j CrossRefPubMedGoogle Scholar
  19. 19.
    van der Heden van Noort GJ, van Delft P, Meeuwenoord NJ, Overkleeft HS, van der Marel GA, Filippov DV (2012) Fully automated sequential solid phase approach towards viral RNA-nucleopeptides. Chem Commun 48(65):8093–8095. https://doi.org/10.1039/C2cc33477a CrossRefGoogle Scholar
  20. 20.
    Filippov D, Kuyl-Yeheskiely E, van der Marel GA, Tesser GI, van Boom JH (1998) Synthesis of a nucleopeptide fragment from poliovirus genome. Tetrahedron Lett 39(21):3597–3600CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hans A. V. Kistemaker
    • 1
  • Jim Voorneveld
    • 1
  • Dmitri V. Filippov
    • 1
  1. 1.Gorlaeus LaboratoriesLeiden Institute of Chemistry, Universiteit LeidenLeidenThe Netherlands

Personalised recommendations