Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense technology. In this paper, we describe the synthesis of GuNA[Me] phosphoramidites bearing other typical nucleobases including adenine (A), guanine (G), and 5-methylcytosine (mC). The phosphoramidites were successfully incorporated into oligonucleotides following the method previously developed for the GuNA[Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or -mC toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides.

Medicinal Applications of Antisense Oligonucleotides: A Review

Antisense technology has emerged as a fast and conceivably high-throughput method for repressing genes due to advancement in knowledge about DNA and RNA physiology. The limitations of antisense oligonucleotide therapy in delivery strategies have been overcome in recent years. Antisense oligonucleotide treatment was effectively applied towards targeting a wide range of therapeutic areas. With ongoing approvals of antisense oligonucleotides, there is an expanding enthusiasm for increasing the utilization of these compounds for curing various infections. This short survey gives a far-reaching comprehension of applications of antisense technology, how they can be utilized therapeutically, and current endeavors to grow new antisense oligonucleotide treatments that will add a forthcoming therapeutic approach for the treatment of various diseases.