Investigation of diastereomers of nonionic analogs of oligonucleotides. III. Complementarily addressed modification of poly(dT) by alkylating derivatives synthesized from individual diastereomers of triethyl esters of tetrathymidylyluridine

Alkylating derivatives of the type of Tp(Et)Tp(Et)Tp(Et)TpU(CHRCl), where CHRCl represents a 2',3'-0-)4-(n-(2-chloroethyl)-N-methylamino)benzylidene) residue, have been synthesized from four individual diastereomers of triethyl esters of tetrathymidylyluridine (Tp(Et))/sub 3/TpU: (CHRCl) (I), Tp'(Et)Tp''(Et)Tp'(Et) x TpU (CHRCl) (II), Tp''(Et)Tp'(Et)Tp''(ET)TpU(CHRCl) (III), and (Tp''(ET))/sub 3/TpU (CHRCl) (IV). The symbols p' and p'' correspond to tetrahedral phosphorus atoms the configuration of which are enantiomeric with respect to one another. The association constants of reagent (I)-(IV) with poly(dA) have been determined from kinetic measurements: 11.6, 24.5, 76.0, and 228.6 M/sup -1/, respectively. For the unaddressed modification of oligo(dA) by the reagent (Me)pU(CHRCl) the competition factor has been determined as 3.5 M/sup -1/, which is an order of magnitude lower than the corresponding magnitude for guanine residues in the composition of a tRNA. It has been shown that the rate of the addressed modification by reagents (I)-(IV) exceeds the rate of nonaddressed modification by factors of 3.3, 6.8, 20.2, and 53.6, respectively.