Synthesis and Properties of Enkephalin Oligonucleotide Conjugates

Abstract

Oligonucleotide derivatives constitute a class of potential therapeutic agents that can be used to target double-stranded DNA, mRNA sequences and even proteins through specific recognition of base sequences and paired with the target sequence. However, the systemic therapeutic use of oligonucleotide is hindered by their poor cellular uptake, lack of stability in intracellular fluid, lack of target specificity and low binding affinity to the target 1-4. Overcoming these obstacles can be realized by many different ways. One approach is conjugation of the oligonucleotide to a peptide that has been suggested as cell delivery vehicles 5-8. Significantly, the oligonucleotides were shown to be taken up by cells when they functioned as noncovalent complexes or covalent conjugates of suitable peptides. Peptide fragments also gain some advantages upon conjugation to oligonucleotides, such as improvement of a certain peptide's ability to fine-tune the oligonucleotide cleavage activity 9. The chosen oligonucleotide CGCACACACGC was a synthetic apurinic undecamer contain 11-basepair, the welldefined system for structural studies 10. Among the miscellaneous peptides, the selected opioidenkephalin has many important physiological functions in animals, such as increase the resistance of immune system and antitoxic of lymphocytes 11-14. Tyrosine was the main amino acid residue for the degradation of enkephalin. Of the degraded