Alpha-morpholino ribonucleoside derivatives and polymers thereof

DETAILED DESCRIPTION OF THE INVENTION The present invention includes a morpholino ribonucleoside derivative having an aldehyde at the 5' position (numbered as shown in FIG.
1) in the alpha orientation.
The aldehyde of this morpholino can be converted to an alcohol, a sulfhydryl, an amine, or an electrophilic moiety retaining the same stereochemical orientation.
Polymers can be assembled from these alpha-morpholino subunits, where the subunits are connected by uncharged linkages one to three atoms long which join the morpholino nitrogen of one subunit to the 5' carbon of another subunit.
A.
Morpholino-Based Subunits FIG.
1 shows the morpholino ring structures on which the polymer subunits are based, where the morpholino carbon atoms are numbered as shown.
As seen in FIG.
1, the ring structure contains a 5' carbon attached to the 4' carbon in the .
alpha.
-orientation.
Each ring structure includes a purine, pyrimidine, or related hydrogen-bonding moiety, P.
sub.
i, attached to the backbone-morpholine moiety through a linkage in the .
beta.
-orientation.
The purine hydrogen-bonding moieties or bases include purines as well as purine-like planar ring structures having a 5-6 fused ring in which one or more of the atoms, such as N3, N7, or N9 is replaced by a suitable atom, such as carbon.
The pyrimidine moieties likewise include pyrimidines as well as pyrimidine-like planar 6-membered rings in which one or more of the atoms, such as N1, is replaced by a suitable atom, such as carbon.
Preferred hydrogen-bonding moieties in the invention include the set of purines and pyrimidines shown in FIGS.
2(1) to 2(9).
Each base includes at least two hydrogen-bonding sites specific for a polynucleotide base or base-pair.
Where the polymers are used for sequence-specific binding to single-stranded polynucleotides, the purine structures 2(1) to 2(3) are designed to bind to thymine or uracil bases; structures 2(7) to 2(8), to guanine bases; structures 2(4) to 2(6) to cytosine bases; and structure 2(9), to adenine bases