Nonionic analogs of oligonucleotide duplexes. Calculations using a molecular mechanics methods of the effect of configuration at the asymmetrical phosphorus atom in phosphonic and triester derivatives of d(TpCH3)6, d(TpOEt)6 on the structure and stability of their complexes with dA6

Molecular mechanical calculations of the optimal structure and relative stability of duplexes of dA6 with non-ionic oligonucleotide analogs of the methylphosphonate d(TpCH3)6 and phosphotriester d(TpOEt)6 have been carried out. Duplexes of dA6 and non-ionic oligonucleotide analogs with Rp enantiomeric configuration of modified phosphorous groups in d(TpCH3) and Sp in d(TpOEt) turned out to be more stable than those with second enantiomeric configurations Sp and Rp, respectively. The main factors of energetic selectivity between Sp and Rp stereoisomers have been found to be steric strains and electrostatic interaction between asymmetric modified phosphate groups and the d-ribose 5' end. NOE generated distances between protons of alkyl substitute and d-ribose H2", H3' have been analysed. The results of the calculations are in agreement with experimental observations.