Compositions and methods for liquid phase oligonucleotide synthesis

A method for preparing an oligonucleotide by liquid phase oligonucleotide synthesis, comprising:

• dissolving a polyvalent hub (PVH) comprising a copolymer comprising one or more acrylamide or acrylate repeating units, and one or more repeating units of Formula (I) in a first solvent to form a reaction matrix,
• wherein:
• X is NR4, S, or O;
• each of R1, R2, R3 and R4 is independently H or C1-C6 alkyl;
• and
• L1 is a heteroalkylene linker comprising one or more oxygen atoms;
• and
• reacting the PVH with one or more nucleoside analogs to form a first bioconjugate comprising a structure of Formula (III):
• wherein
• B1 is a nitrogenous base;
• G1 is a 5′ hydroxyl blocking group;
• Ra is —H, —OH, halogen, —O—(C1-C6 alkyl), —O—(C1-C6 haloalkyl), or —OY, where Y is a 2′ hydroxyl protecting group;
• and
• L3 is a cleavable heteroalkylene linker where one or more carbon atoms is replaced by O, S, N, C(═O) or C(═S).