Novel efficient and expeditious approach for the construction of functionalized nucleic acids is being developed. It is based on aqueous-phase cross-coupling reactions of halogenated nucleoside triphosphates followed by enzymatic incorporation of the modified dNTPs by DNA polymerase. PCR or primer extension experiments are used for the incorporation of the dNTPs to get either duplexes with a high degree of modification or single strand oligonucleotides with just one or several modifications in specific positions. The functionalized nucleic acids are of interest as potential aptamers, DNAzymes, tools in chemical biology and probes in bioanalysis.