Methods And Compositions For Templated Assembly Of Nucleic Acid Specific Heterocompounds

Abstract

The present disclosure is directed methods and products for synthesizing and using targeted templated assembly reactants comprising at least one nucleic acid recognition moiety, at least one selectively-reactive moiety, and at least one effector partial moiety. The nucleic acid recognition moiety can bind a target nucleic acid sequence within a sample. The nucleic acid recognition moiety also can bind the selectively-reactive moiety. Additionally, the effector partial moiety can bind the selectively-reactive moiety to produce an active effector structure. Also disclosed are methods of delivering the targeted templated assembly reactants and active effector structures formed front the targeted templated assembly reactants.

1 . A targeted templated assembly reactant comprising;
 a) at least one nucleic acid recognition moiety that binds a target nucleic acid sequence;   b) at least one effector partial moiety; and   c) at least one selectively-reactive moiety; wherein the reactant is capable of binding a corresponding templated assembly reactant to produce an active effector structure.   
     
     
         2 . The reactant of  claim 1 , wherein the nucleic acid recognition moiety is a nucleic acid-binding oligomer. 
     
     
         3 . The reactant of  claim 1 , wherein the nucleic acid recognition moiety is a nucleic acid oligomer that hybridizes to the target nucleic acid sequence. 
     
     
         4 . The reactant of  claim 1 , wherein the selectively-reactive moiety is biologically inert. 
     
     
         5 . The reactant of  claim 1 , wherein the selectively-reactive moiety is linked to the nucleic acid recognition moiety. 
     
     
         6 . The reactant of  claim 1 , wherein the selectively-reactive moiety is a bio-orthogonal reactive molecule. 
     
     
         7 - 8 . (canceled) 
     
     
         9 . The reactant of  claim 1  further comprising a chemical linker between any of the nucleic acid recognition moiety and the selectively-reactive moiety, and the selectively-reactive moiety and the effector partial moiety. 
     
     
         10 . (canceled) 
     
     
         11 . The reactant of  claim 9 , wherein the chemical linker is at least one of a flexible moiety, cleavage site, and chemical modification site. 
     
     
         12 . The reactant of  claim 1 , wherein the target nucleic acid sequence is selected from a cancer-specific nucleic acid sequence, a viral nucleic acid sequence, a microbial-specific nucleic acid sequence, a differentially expressed gene, a disease-specific nucleic acid sequence, and a fragment, portion or a nucleic acid gene product thereof. 
     
     
         13 . A targeted templated assembly reactant comprising;
 a) at least one nucleic acid recognition moiety;   b) at least one bio-orthogonal moiety; and   c) at least one effector partial moiety.   
     
     
         14 . The reactant of  claim 13 , wherein the nucleic acid recognition moiety is an oligomer selected from the group consisting of DNA nucleotides, RNA nucleotides, phosphorothioate-modified nucleotides, 2-O-alkylated RNA nucleotides, halogenated nucleotides, locked nucleic acid nucleotides (LNA), peptide nucleic acids (PNA), morpholino nucleic acid analogues (morpholinos), pseudouridine nucleotides, xanthine nucleotides, hypoxanthine nucleotides, 2-deoxyinosine nucleotides, other nucleic acid analogues capable of base-pair formation, and combinations thereof. 
     
     
         15 . (canceled) 
     
     
         16 . The reactant of  claim 13 , wherein the bio-orthogonal moiety is selected from the group consisting of an azide, a cyclooctyne, a nitrone, a norbornene, an oxanorbornadiene, a phosphine, a dialkyl phosphine, a trialkyl phosphine, a phosphinothiol, a phosphinophenol, a cyclooctene, a nitrile oxide, a thioester, a tetrazine, an isonitrile, a tetrazole, a quadricyclane, and derivatives thereof. 
     
     
         17 . The reactant of  claim 13 , wherein the effector partial moiety is selected from the group consisting of a peptide, a non-active portion of a peptidomimetic structure, a non-active portion of a drug, and other bioactive compound. 
     
     
         18 . The reactant of  claim 13 , wherein the effector partial moiety is less than 20 kDa. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . The reactant of claim  20 , wherein the chemical linker is selected from the group consisting of an alkyl group, an alkenyl group, an amide, an ester, a thioester, a ketone, an ether, a thioether, a disulfide, an ethylene glycol, a cycloalkyl group, a benzyl group, a heterocyclic group, a maleimidyl group, a hydrazone, a urethane, azoles, an imine, a haloalkyl, a carbamate, and combination thereof. 
     
     
         22 . A method of synthesizing a templated assembly reactant, said method comprising: generating at least one nucleic acid recognition moiety that is capable of binding a target nucleic acid sequence;
 generating at least one selectively-reactive moiety that is capable of binding a corresponding selectively-reactive moiety; and   generating at least one effector partial moiety that is capable of binding a corresponding effector partial moiety to produce an active effector structure.   
     
     
         23 . (canceled) 
     
     
         24 . A method of synthesizing an active effector structure, said method comprising:
 generating at least two templated assembly reactants, wherein said reactants comprise:   at least one nucleic acid recognition moiety that binds a target nucleic acid sequence within a target sample,   at least one selectively-reactive moiety, and   at least one effector partial moiety;   contacting the targeted templated assembly reactants to a target nucleic acid sequence; and   producing an active effector structure.   
     
     
         25 . (canceled) 
     
     
         26 . A method of delivering at least two targeted templated assembly reactants to a pathogenic cell, said method comprising:
 administering a therapeutically effective amount of the targeted templated assembly reactants to the pathogenic cell, wherein said reactants are each comprised of:
 at least one nucleic acid recognition moiety that binds a target nucleic acid sequence within the target pathogenic cell, 
 at least one selectively-reactive moiety, and 
 at least one effector partial moiety; and 
   
       producing at least one active effector structure in the pathogenic cell. 
     
     
         27 . The method of  claim 26 , wherein the method comprising the step of detecting the presence or absence of the target nucleic acid sequence prior to administering the targeted templated assembly reactants. 
     
     
         28 - 35 . (canceled) 
     
     
         36 . An active effector structure formed from a targeted templated assembly product comprising a product of a reaction of
 a) at least two selectively-reactive moieties; and   b) at least one effector partial moiety bound to one of the selectively-reactive moieties.   
     
     
         37 - 40 . (canceled)