Novel nucleoside analogues with fluorophores replacing the DNA base

We describe the preparation and fluorescence properties of a set of new nuc leosides in which a known hydrocarbon or oligothiophene fluorophore replace s the DNA base at C(1) of the deoxyribose moiety (see 3a-f). These compound s are potentially useful as probes in the study of the structure and dynami cs of nucleic acids and their complexes with proteins. in addition, they ma y find use as fluorescent labels for nucleic-acid-based biomedical diagnost ics methods. The fluorophores conjugated to deoxyribose at C(1) in the alph a-D-form include terphenyl, stilbene, terthiophene, benzoterthiophene, and pyrene. Also included is a non-fluorescent spacer in which cyclohexene repl aces the DNA base. The nucleosides are derived from brominated fluorophore precursors and Hoffer's 2-deoxy-3,5-di-O-(p-toluoyl)-D-ribofuranosyl chlori de. The emission maxima of the free nucleosides range from 345 to 536 nm. A lso described are the 5'-(dimethoxytrityl) 3'-O-phosphoramidite derivatives 5a-f, suitable for incorporation into oligonucleotides by automated synthe sizers.