Abstract
In this work, we report the synthesis of a novel Fmoc-protected nucleoaminoacid, based on 4-piperidinyl glycine, carrying the DNA nucleobase on the secondary amino group, suitable for the solid-phase synthesis of nucleopeptides. After ESI–MS and NMR characterization this building block was used for the assembly of a thymine-functionalized tetrapeptide, composed of 4-piperidinyl glycine and l-arginine moieties alternated in the backbone. The ability to interact with RNA and the efficiency in interfering with the reverse transcription of eukaryotic mRNA of the novel nucleo-tetrapeptide found in this study are in favour of the employment of chiral nucleopeptides based on alternate 4-piperidinyl glycine/l-arginine backbone in biomedicine.
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Abbreviations
- Ac2O:
-
Acetic anhydride
- Boc:
-
tert-Butoxycarbonyl
- DCM:
-
Dichloromethane
- DIEA:
-
N,N-Diisopropylethylamine
- DMF:
-
N,N-Dimethylformamide
- DMSO:
-
Dimethylsulfoxide
- Fmoc:
-
9-Fluorenylmethoxycarbonyl
- GAPDH:
-
Glyceraldehyde 3-phosphate dehydrogenase
- HATU:
-
O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate
- MBHA:
-
4-Methylbenzhydrylamine
- NMP:
-
4-Methylpyrrolidone
- Pbf:
-
2,2,4,6,7-Pentamethyldihydrobenzofuran-5-sulfonyl
- TAE:
-
Tris-acetate-EDTA
- TCH2COOH:
-
Thymin-1-yl acetic acid
- TFA:
-
Trifluoroacetic acid
- TIS:
-
Triisopropyl silane
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Acknowledgments
We thank Prof. Antonio Roviello and Dr. Anna Cioccia for their precious suggestions and Mr. Leopoldo Zona for his invaluable technical assistance. We are also grateful to the institutions that supported our laboratory (Consiglio Nazionale delle Ricerche and Università degli Studi di Napoli ‘Federico II’).
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Roviello, G.N., Crescenzo, C., Capasso, D. et al. Synthesis of a novel Fmoc-protected nucleoaminoacid for the solid phase assembly of 4-piperidyl glycine/l-arginine-containing nucleopeptides and preliminary RNA interaction studies. Amino Acids 39, 795–800 (2010). https://doi.org/10.1007/s00726-010-0532-4
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DOI: https://doi.org/10.1007/s00726-010-0532-4