Complexation of single strand telomere and telomerase RNA template polyanions by deoxyribonucleic guanidine (DNG) polycations: Plausible anticancer agents

Cancerous cell immortality is due to relatively high concentrations of telomerase enzyme which maintains telomere sequence during cell division. Deoxyribonucleic guanidine (DNG) is a positively charged DNA analog in which guanidine replaces the phosphordiester linkage of DNA. Mixed sequences of DNG and DNA oligonucleotides are referred to as chimera. Complexation of DNG and chimeric polycations with the complementary negatively charged non-coding telomere single strand d(5′-TTAGGG-3′)n and the 11-base telomeric RNA template (5′-CUAACCCUAAC-3′) in the active site of telomerase has been studied. Calculated by ensemble sampling simulations in GBMV solvent model, we found that binding of complementary DNG hexamer with telomere is favored over that of DNA-telomere by ∼106-fold and binding of chimera hexamer is favored by ∼104-fold. Binding of complementary DNG with telomeric RNA is favored by 43 kcal/mol over telomere substrate binding with telomeric RNA.