Sequence-specific binding polymers for duplex nucleic acids

A method for coupling a first free or polymer-terminal subunit having one of the following subunit forms:

• ##STR33## where R.sub.i is a planar ring structure having two or more hydrogen-bonding sites, with a second free or polymer-terminal subunit having one of the following subunit forms:
• ##STR34## where Z is a 2-atom or 3-atom long moiety, said method comprising:
• i) oxidizing the first subunit to generate a dialdehyde intermediate;
• ii) contacting the dialdehyde intermediate with the second subunit under conditions effective to couple a primary amine to a dialdehyde;
• and
• (iii) adding a reducing agent effective to give a coupled structure selected from the following forms:
• ##STR35##

A subunit composition for use in forming a polymer composition effective to bind in a sequence specific manner to a target sequence in a duplex polynucleotide, comprising one of the following subunit structures:

• ##STR36## where R' is H, OH, or O-alkyl;
• the 5'-methylene has a .beta. stereochemical orientation in subunit forms (a), (c), and (d) and a uniform stereochemical orientation in subunit form (b);
• X is hydrogen or a protective group or a linking group suitable for joining the subunits in any selected order into a linear polymer;
• Y is a nucleophilic or electrophilic linking group suitable for joining the subunits in any selected order into a linear polymer;
• and X and Y together are such that when two subunits of the subunit set are linked the resulting intersubunit linkage is 2 or 3 atoms in length and uncharged;
• Z is a 2-atom or 3-atom long moiety;
• and, R.sub.i, which may be in the protected state and has a .beta. stereochemical orientation, is selected from the group consisting of planar bases having the following skeletal ring structures and hydrogen bonding arrays, where B indicates the aliphatic backbone moiety:
• ##STR37## where the * ring position may carry a hydrogen-bond acceptor group;
• and X may be a moiety effective to afford discriminative binding on the basis of the moiety at the 5 position of the pyrimidine of the target base-pair;
• or, where R.sub.i is selected from the group consisting of planar bases having the following skeletal ring structures and hydrogen bonding arrays, where B indicates the aliphatic backbone moiety:
• ##STR38## where the * ring position may carry a hydrogen-bond donating group;
• and X may be a moiety effective to afford discriminative binding on the basis of the moiety at the 5 position of the pyrimidine of the target base-pair.

A subunit composition for use in forming a polymer composition effective to bind in a sequence specific manner to a target sequence in a duplex polynucleotide, comprising one of the following subunit structures:

• ##STR39## where the 5'-methylene has a .beta. stereochemical orientation in subunit forms (b), and (c) and a uniform stereochemical orientation in subunit form (a);
• X is hydrogen or a protective group or a linking group suitable for joining the subunits in any selected order into a linear polymer;
• Y is a nucleophilic or electrophilic linking group suitable for joining the subunits in any selected order into a linear polymer;
• and X and Y together are such that when two subunits of the subunit set are linked the resulting intersubunit linkage is 2 or 3 atoms in length and uncharged;
• Z is a 2-atom or 3-atom long moiety;
• and, R.sub.i, which may be in the protected state and has a .beta. stereochemical orientation, is selected from the group consisting of planar bases having the following skeletal ring structures and hydrogen bonding arrays, where B indicates the aliphatic backbone moiety, the starred atom is not a hydrogen bond acceptor, and W is oxygen or sulfur:
• ##STR40##