Polynucleotides protecting groups

K. Tajima and T. Hata. Simple Protecting Group Protection-Purification Handle for Polynucleotide Synthesis, II. Bull. Chem. Soc. Jpn., 45, 2608 (1972). 

ODMT (ODMTr) is the 4,4 -dimethoxytrityl group, a common -OH protecting group for the carbohydrate moieties in syntheses of polynucleotides. 

Solid-phase synthesis is usually done on a silica support with a covalently attached succinamide as shown in Eq. 5-25. The first nucleotide at the 3 end of the chain to be synthesized is attached by an ester linkage to the bound succinamide (step a, Eq. 5-25). The 5 -protecting group is removed in step b and the 5 -OH reacts with the activated phosphine of the second nucleotide (step c, Eq. 5-25). Steps b and c are then repeated as often as necessary to complete the chain. The finished polynucleotide can be removed from the solid support, the cyanoethyl groups removed... 

Fig. 1. Light-directed synthesis of polynucleotide probe arrays. Exposure to light through a photolithographic mask is used to remove protecting groups from surface sites in pre-defined regions of a functionalized glass substrate. A solution of an activated polynucleotide building block is then applied, which reacts specifically in the exposed regions of the substrate. Repeated cycles of illumination-deprotection and monomer coupling are used to construct a two-dimensional array of probe sequences...

After the desired sequence is completed, the polynucleotide is released from the solid support, and protecting groups are removed via hydrolysis with ammonium hydroxide. The DNA is purified by gel electrophoresis or hplc and characterized by mass spectrometry. Similar methods are used to synthesize RNA oligomers, although the 2 -OH group on the ribose ring must be protected. 

An unwanted side reaction of the triester approach has presented itself during polynucleotide synthesis (i.e., beyond the dinucleotide stage) internucleotide cleavage. This has been observed to a significant extent during the removal of aryl protecting groups with either hydroxide or fluoride ... 

Jones, R A., Fritz, H J., and Khorana, H G. (1978) Studies on polynucleotides 147 Use of the lipophilic rerr-butyldiphenylsilyl protecting group in synthesis and rapid separation of polynucleotides. Biochemistry 17, 1268-1278 Mishra, R. K. and Misra, K. (1988) Protecting groups as purification tool in large-scale synthesis of small oligodeoxynucleotides Indian J, Chem Sect. B, 27B, 817-820. 

The possibilities of N-(dialkylphosphoryl)amino acids for the prebiotic syntheses of peptides and polynucleotides have been studied in a series of papers [24,116-122], However, it must be emphasized that the phosphoryl group does not behave as an amino-activating group, the hydrolysis of which would be coupled to peptide bond formation. Actually, further peptide elongation requires the subsequent hydrolysis of the N-terminal phosphoryl group of the ligated product. In the presence of an amino acid ester, dipeptide esters 16 with an unreacted N-phosphoryl protection are formed, support-... 

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