HELICAL COMPLEXES OF OLIGONUCLEOTIDES WITH DERIVATIVES OF OLIGOAMIDES- SPECIFICITY OF COMPLEMENTARY RECOGNITION

The method of molecular mechanics with an AMBER 3.0 computer software package, supplemented By specially developed subprograms, was used to carry out a conformational analysis of hybrid double helices with nonc anonical H-bonds composed of oligodeoxyribonucleotide and oligoamide f ragments (dT)(5) .(pT)(5) (1) and (dA)(4)(dT)(2)(dA)(4) .(dT)(3)(pT)(4 )(dT)(3) (2). The purpose of the work was to perform a pre-synthesis e stimation of Watson-Crick specificity of binding specially constructed oligomers, which carry oligoamide inserts of 2-aminoethylglycine unit s in the center, connected to nitrogen bases through a methylenecarbon yl group. A comparison of helical parameters and potential energies in optimized structures of hybrid oligonucleotides with noncanonical T . T-pairs with the energies of analogs containing only canonical A . T- pairs showed that disruption of Watson-Crick complementarity results i n a crucial distortion of hybrid double helices, which leads to their destabilization. For this reason, the expected probability of mispairi ng of oligonucleotides is low for the proposed analogs of oligonucleot ides carrying oligoamide inserts. Hence, the synthesis of these oligon ucleotides is promising for creating reagents with selective action on single-stranded oligonucleotides inside cells.