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

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.

Natural and artificial binders of polyriboadenylic acid and their effect on RNA structure

“…Furthermore, Pradhan et al [47] recently found that the phenazinium dye safranin T (Figure 8) recognised singlestranded poly(rA) with great affinity, while it is not able to bind the double-stranded form of the same RNA. Interesting binding results relative to the interaction with poly(rA) of artificial compounds, such as benzodifuran (Figure 9), cationic peptides and nucleoamino acid-based molecules were found by Roviello et al [48][49][50][51][52][53][54][55][56], Moggio et al [57] and Saghyan et al [58]. In particular, regarding the interaction with nucleopeptides ( Figure 10), a significant role was played not only by the molecular recognition of complementary nucleobases, but also by the electrostatic interactions occurring between anionic phosphodiester moieties and the cationic residues present in the nucleo-peptide structures.…”

Willardiine and Its Synthetic Analogues: Biological Aspects and Implications in Peptide Chemistry of This Nucleobase Amino Acid

“…Refs. [ 82 , 83 , 84 , 85 ] Nonetheless, nucleoamino acid moieties are found in the natural peptidyl nucleosides [ 86 ], molecules that play a key role in biology and therapy, while a plethora of synthetic nucleoamino acids were developed as building blocks of nucleopeptides [ 87 , 88 , 89 , 90 , 91 , 92 ].…”

Enantioselective Synthesis of D‐α‐(Uracil‐5‐yl)glycine Derivatives and Their Racemization‐Free Incorporation into a Model ­Peptide

“…[14] They are able to interact with complementary RNA, enhance peptide-peptide recognition, and inhibit the activity of MMLV (Moloney murine leukemia virus) reverse transcriptase by the formation of complexes with polyA at the primer site. [15][16][17] To date, most studies have used NBAs derived from alanine or homoalanine. The corresponding glycine-derived NBAs have been investigated to a much lesser extent, since they have not been synthetically accessible in enantiomerically pure form.…”