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Synthesis, spectroscopic studies and biological activity of a novel nucleopeptide with Moloney murine leukemia virus reverse transcriptase inhibitory activity

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Abstract

In this work, we report the synthesis of an alternate nucleo-alpha,epsilon-peptide based on l-lysine moieties, an in vitro study of its biological activity, and spectroscopical binding studies between the novel nucleopeptide and Moloney murine leukemia virus reverse transcriptase as well as RNA. An alternate homothymine hexamer was synthesized by a straightforward solid phase route starting from commercial materials, purified by RP-HPLC and characterized by ESI-MS. The efficiency of the novel nucleo-alpha,epsilon-peptide in interfering with the reverse transcription of eukaryotic mRNA and the noteworthy enzymatic resistance demonstrated by specific assays are in favor of the employment of this nucleopeptide in novel biomedical strategies.

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Abbreviations

Ac2O:

Acetic anhydride

DBU:

1,8-Diazabicyclo[5.4.0]undecene

DIEA:

N,N-Diisopropylethylamine

DMF:

N,N-Dimethylformamide

Fmoc:

9-Fluorenylmethoxycarbonyl

HATU:

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate

PyBOP:

Benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate

PTFE:

Polytetrafluoroethylene

TAE:

Tris–acetate–EDTA

TFA:

Trifluoroacetic acid

TMP:

2,4,6-Trimethylpyridine

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Acknowledgments

The authors would like to thank Dr. Andrea De Cristofaro and Mr. Leopoldo Zona for their invaluable assistance. We are also grateful to the institutions that supported our laboratory (Consiglio Nazionale delle Ricerche and Università degli Studi di Napoli ‘Federico II’) and MIUR (FIRB RBRN07BMCT).

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Authors and Affiliations

  1. Istituto di Biostrutture e Bioimmagini, CNR, via Mezzocannone 16, 80134, Naples, Italy

    Giovanni N. Roviello, Sonia Di Gaetano, Annalisa Cesarani & Enrico M. Bucci

  2. Dipartimento delle Scienze Biologiche, Università di Napoli “Federico II”, 80134, Naples, Italy

    Domenica Capasso & Carlo Pedone

Authors
  1. Giovanni N. Roviello
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  2. Sonia Di Gaetano
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  3. Domenica Capasso
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  4. Annalisa Cesarani
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  5. Enrico M. Bucci
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  6. Carlo Pedone
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Corresponding author

Correspondence to Giovanni N. Roviello.

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Roviello, G.N., Gaetano, S.D., Capasso, D. et al. Synthesis, spectroscopic studies and biological activity of a novel nucleopeptide with Moloney murine leukemia virus reverse transcriptase inhibitory activity. Amino Acids 38, 1489–1496 (2010). https://doi.org/10.1007/s00726-009-0361-5

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