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Recently, several oligonucleotide drugs have been approved and are being used in clinical applications. Oligonucleotide drugs are generally composed of about 20 nucleotides, but the natural oligonucleotide structure is not suitable for drugs from the perspectives of biostability and affinity to the target. Therefore, chemically modified oligonucleotides are synthesized and utilized as drug candidates.
The phosphoramidite method is standard for oligonucleotide synthesis. In this method, one nucleotide addition is conducted by a synthetic cycle using the following three steps: i) coupling of a phosphoramidite and an oligonucleotide at the 5′-OH of the terminal nucleotide with an activator such as 1H-tetrazole and capping of the unreacted hydroxy group; ii) oxidation or sulfurization of the phosphite moiety; and iii) deprotection of the DMT group. This cycle is performed by an automated synthesizer and oligonucleotides can be prepared quickly and easily with this system. Chemically synthesized DNA is becoming important as a primer for the PCR method, an antisense molecule, or an element of a DNA computer.
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