Abstract
The advantages and disadvantages of existing approaches to the synthesis of oligodeoxyribonucleotides (ODN) are discussed focusing on large-scale methods. The liquid phase and solid supported synthesis and the synthesis on soluble polymers are discussed. Different problems concerning the methods and implementation of the ODN synthesis are outlined depending on goals of using target oligomers.
Highlights
The interest in nucleic acid chemistry is due to an increasing need of synthetic oligomers of natural structure and their modified derivatives and analogs as indispensable research tools in molecular biology and fundamental medicine [1,2,3,4,5,6,7].Nucleic acids are natural single- or double-stranded polymers comprising deoxyribo- or ribonucleosides linked by the phosphoric acid residues (Figure 1)
This minireview considered the major problems of the modern ODN synthesis
At the early development stages of the ODN synthesis, the progress in the nucleic acid chemistry gave a powerful impetus to the development of the fundamental research in molecular biology [9,10]
Summary
The interest in nucleic acid chemistry is due to an increasing need of synthetic oligomers of natural structure and their modified derivatives and analogs as indispensable research tools in molecular biology and fundamental medicine [1,2,3,4,5,6,7]. The main task in the synthesis of these compounds is the binding of the monomer units in the specified order forming phosphodiester internucleotide bonds. After completion of the assembly of an oligomer by the block method or by the sequential addition of monomers (Figure 2), the removal of all protective groups and purification the product are required. - temporary protective groups coupling сleavadge from solid support deprotection purification. All steps of these processes must be very efficient to achieve an acceptable yield of a target oligomer. The synthesis of hundreds and thousands of different oligomers in small quantities (up to 1 mg of each) and the synthesis of a particular oligomer in large amount (more than 100 mg) pose quite different tasks for chemists. We will outline important aspects of the modern ODN synthesis highlighting the problems of the synthesis of both oligomers of a large variety in small qauntities and an oligomer of a certain sequence in a large amount
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