2′-N-Guanidino,4′-C-ethylene bridged thymidine (GENA-T) modified oligonucleotide exhibits triplex formation with excellent enzymatic stability

Abstract

Here we present the synthesis and characterization of a new 2′-N-Guanidino,4′-C-ethylene bridged thymidine (GENA-T) modified oligonucleotide possessing North-locked sugar conformation. Incorporation of GENA-T nucleotide though did not change the thermal stability of the oligonucleotides toward the complementary RNA; it significantly increased the stability of the parallel triplex at pH 7. The melting temperature of the triplex was increased by +9.5 °C as compared to that of the isosequential unmodified sequence. Moreover this modification imparted exceptional nuclease stability to the oligonucleotides for over 33 h. This study clearly demonstrates that GENA-T modified oligonucleotides could improve triplex formation with phenomenal enzymatic stability and could be used for various biomedical applications.