Poly(oligonucleotide)

Abstract

Here we report the preparation of poly(oligonucleotide) brush polymers and amphiphilic brush copolymers from nucleic acid monomers via graft-through polymerization. We describe the polymerization of PNA-norbornyl monomers to yield poly-PNA (poly(peptide nucleic acid)) via ring-opening metathesis polymerization (ROMP) with the initiator, (IMesH2)(C5H5N)2(Cl)2RuCHPh.1 In addition, we present the preparation of poly-PNA nanoparticles from amphiphilic block copolymers and describe their hybridization to a complementary single-stranded DNA (ssDNA) oligonucleotide.

Figure 1

Synthesis and characterization of a poly(oligonucleotide). (A) PNA-norbornyl monomer (PNA-Nb) polymerized using ROMP initiator (IMesH₂)(C₅H₅N)₂(Cl)₂Ru=CHPh (“Ru”) to form poly-PNA homopolymer, I, and poly-PNA block copolymer, II. (B) Representative percent conversion for I determined by the disappearance of the olefin signal associated with PNA-Nb in ¹H NMR. (C) Representative SEC-MALS for II. M_n = 28,270 indicating a degree of polymerization of 5 for the PNA block.

Scheme 1. Known Methods for the Incorporation of Multiple Nucleic Acids or Nucleobases into Polymers

(A) Post-polymerization modification of a polymer with a nucleic acid.⁻ (B) Polymerization of a pyrimidine base as a modified monomer.⁻

Figure 2

Structures of monomers used for block copolymer preparation.

Figure 3

Poly-PNA amphiphile II was dialyzed from DMSO into H₂O to generate nanoparticles. (A) DLS data indicating a hydrodynamic radius of 25 nm. (B) T_m of PNA-NP with a complementary DNA sequence was found to be 58.1 °C. (C) Negative-stained TEM of PNA-NP provided evidence of spherical 20 nm diameter nanoparticles. Atomistic models of (D) II and (E) PNA-NP. II is shown in a conformation present within PNA-NP.