Abstract
A synthetic approach leading to novel‐type modified oligothymidylates containing an isosteric, isopolar, enzyme‐stable C3′‐O‐P‐CH~2~‐O‐C4″ phosphonate alternative to phosphodiester internucleotide bond was elaborated. The suitable monomers were prepared from 4′‐phosphonomethoxy derivatives of α‐L‐threo and β‐D‐erythro‐2′,5′‐dideoxythymidine, which were considered interesting as structurally related to nucleoside 5′‐monophosphates. The phosphotriester method was applied to the automated synthesis of both homooligomeric phosphonate 15‐mer chains and alternating phosphonate–phosphate constructs. The fully modified homooligomers did not hybridize while homooligomers with alternating sequences containing α‐L‐threo–configured units (but not β‐D‐erythro–) showed a significant decrease in T~m~ values in comparison with natural dT~15~. For a comparative study, phosphodiester 4′‐CH~3~–substituted oligothymidylate was synthesized and physical studies (NMR, CD, MDS modeling) were undertaken to shed more light on the changes in conformational behavior arising from the chosen structural alterations. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 400–413, 2006
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]