ABSTRACT
Covalent bonds between nucleic acids and amino acids, peptides, or proteins occur naturally in the genomes of certain RNA and DNA viruses. In these molecules, the protein-nucleic acid linkage occurs through a 5' -phosphodiester bond to serine, tyrosine, or threonine [1,2]. Other naturally occurring examples of RNA-amino acid conjugates are the aminoacyl-transfer RNAs (tRNAs), in which the amino acids are esterified to the 2'- or 3' -hydroxyl group of tRNA [3,4]. These naturally occurring conjugates are called nucleoproteins and nucleopeptides. Moreover, interest in oligonucleotide-peptide conjugates (also called oligonucleotide-peptide chimeras or oligonucleotidepeptide hybrids) has grown. They are chimeras constituted by oligonucleotides that are connected to peptide sequences and are produced to add some of the biological or biophysical properties of peptides to synthetic oligonucleotides. They are different from peptide nucleic acids (PNAs) because PNAs are not formed by natural amino acids but are oligonucleotide analogues with modified backbones. They are also different from nucleopeptides because they are not found in nature. From the synthetic point of view, nucleopeptides and oligonucleotide-peptide conjugates are similar. In fact, nucelopeptides may be considered a particular case of oligonucleotide-peptide conjugates in which the linkage between peptide and oligonucleotide is performed through the side chain or the carboxylic function of particular amino acids.
