Carbohydrate-Functionalized Locked Nucleic Acids: Oligonucleotides with Extraordinary Binding Affinity, Target Specificity, and Enzymatic Stability

Three different C5-carbohydrate-functionalized LNA uridine phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides. C5-Carbohydrate-functionalized LNA display higher affinity toward complementary DNA/RNA targets (ΔTm/modification up to +11.0 °C), more efficient discrimination of mismatched targets, and superior resistance against 3′-exonucleases compared to conventional LNA. These properties render C5-carbohydrate-functionalized LNAs as promising modifications in antisense technology and other nucleic acid targeting applications.