“Molecular Chameleons”. Design and Synthesis of C-4-Substituted Imidazole Fleximers

Abstract

The synthesis of two flexible nucleosides is presented. The "fleximers" feature the purine ring system split into its imidazole and pyrimidine components. This modification serves to introduce flexibility to the nucleoside while still retaining the elements essential for molecular recognition. As a result, these structurally innovative nucleosides can more readily adapt to capricious binding sites and, as such, should find use for investigating enzyme-coenzyme as well as nucleic acid-protein interactions.

Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity

“…This analogue was chosen due to the versatility of compound 10 . As had been previously published by our group 13 , it was hypothesized it would be possible to obtain both the Flex-xanthosine and Flex-guanosine analogues from 10 (Scheme 2). Preparation of the boronic acid 9 followed established procedures 21 and was used immediately without further characterization.…”

Flexible Nucleobase Analogues: Novel Tools for Exploring Nucleic Acids

“…This allows for rotation, while still retaining the elements essential for base pairing and molecular recognition (Seley et al 2002(Seley et al , 2005. A number of different possibilities for connectivity exist; however, the Seley-Radtke studies have focused on A and B shown in Fig.…”

Synthesis of distal and proximal fleximer base analogues and evaluation in the nucleocapsid protein of HIV-1

“…For some time, the Seley-Radtke group has designed and synthesized various classes of flexible purine nucleos(t)ides, or “fleximers”. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 These novel nucleosides were designed to investigate how flexibility in the nucleobase could potentially affect receptor-ligand recognition and function. In addition, their flexible design allows them to overcome issues with binding site mutations thus retaining their activity.…”