Stereospecific Synthesis of P-Chiral Analogs of Oligonucleotides
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As has been emphasized in corresponding chapters of this book, isotopic or elemental replacement of any of two nonbridging oxygens attached to internucleotide phosphorus atom(s) by substituent X (Fig. 1 ) creates, by virtue of asymmetry, new center(s) of chirality and results in the formation of m diastereoisomers of the oligonucleotide’s congener. The number m is determined by the number n of modified phosphates, according to formula m = 2 n . With the exception of diastereoisotopomers (X= 17 O or 18 O), which are nonseparable by any so-far-developed separation technique, separation of diastereoisomeric oligonucleotides containing modified phosphates (Fig. 1 , X = S; Se; C 2 H 5 O-; CH 3 -; ArNH-; R 2 N-) has been achieved by means of chromatographic techniques. Effectiveness of the separation depends, however, on the number of modifications within the oligonucleotide chain and is practically limited to n =l,2. Achievements in this field have been exhaustively summarized by Zon ( 1 ).
Fig. 1. Modifications to the DNA phosphate groups.
