Synthesis and characterization of nucleic acid-(co)polymer conjugates: application to diagnostics

This paper provides a survey of the synthesis of oligodeoxyribonucleotides (ODNs)–(co)polymer conjugates for application to diagnostics. Reactive copolymers containing various chemical functions (carboxylic acid groups under the form of activated esters or aldehyde) were used to covalently link ODNs. It was found that this immobilization reaction was dependent upon several parameters including the chemical reactivity of the functional group, the structural parameters (conformation) of the polymer, and the hydrogen bonding capability between the two macromolecular partners. Analysis of the conjugation products by size exclusive chromatography – light scattering displayed higher molecular weights than expected because of a concomitant aggregation process resulting from either hydrogen bonding between ODNs and polymer chains or side reactions from heterocyclic base amino groups. The extent of this aggregation process was dependent on the chemical nature of the polymer and base composition of the probes and it could be partly or totally avoided upon decreasing the capacity of the nucleic acids to form hydrogen bonds. These conjugates were tested in nucleic acid detection and they were shown to improve assay in both capture and signal efficiency for a long double-stranded DNA.